RARE DISEASE
Retinitis pigmentosa
Retinitis pigmentosa
Retinitis pigmentosa
Drug discovery
97
drugs
With orphan designations
Overview
Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive degeneration of rod and cone photoreceptors, leading to night blindness, peripheral vision loss, and eventual central vision impairment. Caused by mutations in over 60 genes, RP typically manifests in childhood/adolescence and progresses variably. No cure exists, but therapeutic strategies aim to slow progression (e.g., vitamin A supplementation, gene therapy for specific mutations) and manage complications (e.g., cataracts, macular edema) [1][2][6][11].
Burden
Leading cause of inherited blindness; 5–7% of new blindness cases in Western countries [4][7].
Legal blindness in ~40% by age 40; severe quality-of-life decline, unemployment, and caregiver strain [4][7][16].
Annual U.S. economic burden exceeds $1 billion, including direct healthcare and indirect productivity losses [4][16].
Therapies
Gene therapy: FDA-approved voretigene neparvovec (RPE65 mutations) [13][17]; experimental therapies (e.g., QR-421a for USH2A) in trials [13].
Supportive care: Vitamin A palmitate (15,000 IU/day) to slow progression; avoid high-dose vitamin E [1][11][18].
Low-vision aids: Retinal prostheses, orientation training, and adaptive technologies [6][11][15].
Categories: rare genetic diseases, rare neurological diseases, rare ophthalmic disorders
Research Papers
3,399 drug discovery papers about Retinitis pigmentosa, with 2 first-in-class and 56 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
3,399 drug discovery papers about Retinitis pigmentosa, with 2 first-in-class and 56 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-13 | N-acetylcysteine suppresses retinal defects in Drosophila models of SNRNP200-associated retinitis pigmentosa.
Retinitis Pigmentosa (RP) is an inherited retinal degenerative disease that affects 1 in 4000 individuals worldwide and can lead to complete blindness. Early stages of RP involve death of rod photoreceptors via apoptosis, causing loss of peripheral and night vision, which is followed by death of cone photoreceptors, leading to loss of central and daytime vision. Mutations in over 300 genes cause RP. Many of these genes encode retina-specific proteins; however, some encode globally expressed proteins, such as pre-mRNA splicing factors. This study is focused on mutations in the SNRNP200 gene encoding a core pre-mRNA splicing factor. The pathological mechanisms of SNRNP200-associated RP are not well understood and treatments are limited. An approach to study pathogenic mechanisms is to utilize model organisms. Therefore, we developed Drosophila models in which RP-causing mutations were introduced into the Drosophila melanogaster orthologue Snrnp200. In addition, we used RNAi to knock-down Snrnp200 in the developing eye. Depletion of Snrnp200 caused an adult rough eye phenotype due to apoptosis of cells in the retina. When human RP-causing mutations were modeled in Drosophila Snrnp200, they resulted in abnormal retinal electrophysiology and defective patterning of photoreceptors. Further analysis of the photoreceptors revealed mitochondrial defects and altered expression of genes related to redox homeostasis. Consistent with these changes, treatment with the antioxidant N-acetylcysteine (NAC) partially suppressed the photoreceptor defects. Taken together, these findings established a new genetic model for studies of splicing-factor associated RP that recapitulates aspects of the human disease and suggests that antioxidants might serve as a treatment for individuals with SNRNP200-associated RP.
2026-08-10 | The efficacy and safety of oral and topical carbonic anhydrase inhibitors for the treatment of macular edema secondary to retinitis pigmentosa: a systematic review and meta-analysis.
Carbonic anhydrase inhibitors (CAIs) are commonly used to treat macular edema (ME) secondary to retinitis pigmentosa (RP). This meta-analysis aims to better understand the efficacy of topical or oral CAIs therapy and to summarize the rates of improvement and recurrence of ME, as well as adverse events. A systematic review was conducted by searching PubMed, Web of Science, Embase, CENTRAL, CNKI, Wanfang, and VIP databases with no language filters applied. Eligible studies were those investigating topical or oral CAIs for the treatment of ME secondary to RP. Central macular thickness (CMT) and best-corrected visual acuity (BCVA) were extracted as the primary outcome measures for comprehensive analysis. This meta-analysis identified a total of 16 eligible studies, encompassing 267 patients (487 eyes). Moderate certainty evidence from RCTs demonstrated that oral CAIs significantly improved BCVA, whereas topical CAIs showed no statistically significant effect. Low to moderate certainty evidence from non-RCTs revealed that both oral and topical CAIs significantly improved CMT (both P < 0.001). This meta-analysis indicates that oral CAI therapy significantly reduces CMT and improves BCVA in patients with RP, whereas the effect of topical CAIs on BCVA remains uncertain. A large-scale, prospective randomized controlled trial would be ideal to further investigate the differences in clinical efficacy and adverse events between oral and topical CAIs in this patient population.
2026-07-30 | Gap junctions form bridges between bench studies and clinical ophthalmology.
In retinal neurodegenerative disorders, the initial degeneration of primary target cells is frequently followed by a phenomenon known as the bystander effect, wherein neighboring, initially unaffected cells also undergo degeneration. This secondary cell death can exceed the number of directly insulted cells (Frantseva et al., 2002a,b; de Rivero Vaccari et al. 2007; Wang et al. 2010; Park et al. 2011; Akopian et al. 2014; O'Brien and Bloomfield, 2018). Although the precise mechanisms underlying the bystander effect remain incompletely understood, gap junctions (GJs) have been implicated in mediating the spread of pro-death signals from injured to adjacent cells. Consequently, GJs have become a focal point in recent research, with GJ blockade proposed as a neuroprotective strategy in progressive retinal diseases, such as diabetic retinopathy, ischemia, and glaucoma. However, GJs are essential in physiological neuronal communication, and their prolonged inhibition may disrupt visual processing (Bloomfield and Völgyi, 2009; Völgyi et al., 2013; O'Brien and Bloomfield, 2018), thereby limiting the therapeutic utility of GJ blockades in the treatment of chronic retinal conditions. Considering this, we propose an alternative hypothesis: rather than solely contributing to neurodegeneration, GJs may also support cell survival by facilitating the intercellular transmission of protective molecules (termed here as 'health-signals') that counteract apoptotic cascades and possibly attenuate the primary insult itself. In this framework, GJs could disseminate "health signals" across the retinal network, suggesting that co-administering neuroprotective agents with GJ permeability enhancers might amplify their therapeutic reach. While this hypothesis assumes that key endogenous molecules can cross GJs, their specific properties and transjunctional dynamics remain poorly understood. This review consolidates current knowledge on GJ-mediated communication and explores its clinical utility in retinal neuroprotection.
2026-07-29 | Metabolomics Effects of Folding Correction in Retinitis Pigmentosa Rhodopsin Mutant P23A.
Retinitis pigmentosa (RP) is a hereditary retinal degeneration disorder often caused by mutations in the rhodopsin gene, leading to photoreceptor death and vision loss. While structural misfolding of rhodopsin is a known contributor to disease pathology, the mechanisms of its cellular and in particular metabolic consequences are poorly understood. To study the direct effects of rhodopsin misfolding and structural rescue on cellular metabolism, we used the P23A mutant and its N2C/D282C stabilized counterpart as a structural tool to assess how differences in folding stability relate to measurable changes at the metabolite level. The engineered cysteine pair allows the formation of a disulfide bond restoring structural integrity and reinforcing the stable seven-transmembrane bundle. We used untargeted Gas Chromatography-Mass Spectrometry (GC-MS) metabolomics analysis conducted in inducible rhodopsin-expressing cell lines, providing a broad and general profiling of metabolic pathway alterations in response to the expression of RP mutants and their structurally rescued counterparts. Principal component analysis, hierarchical clustering, and K-means clustering revealed distinct metabolic signatures associated with each rhodopsin-expressing cell line, demonstrating a highly significant effect of genotype on global metabolite composition (F = 71.679; R2 = 0.93724; p = 0.001). Pairwise comparisons and background-subtracted analyses identified consistent alterations in arginine and proline metabolism, glutathione metabolism, and the TCA cycle, nucleotide, amino acid metabolism, redox regulation, and mitochondrial function in cells expressing misfolded P23A. Pathway enrichment highlighted key metabolites in the respective pathways as candidate biomarkers for the rhodopsin P23A mutation. As this study employs a non-retinal cell system, the observed metabolic changes reflect conserved responses to rhodopsin misfolding and proteostatic stress in the ER rather than a direct model of rod cell degeneration. Our findings support the hypothesis that there is a biochemical link, most likely the UPR, between rhodopsin folding/misfolding status and metabolic homeostasis and suggest that targeted metabolic modulation may offer a complementary therapeutic avenue for treating RP.
2026-07-29 | A cargo receptor entrapment complex is a therapeutic node for genetically and clinically distinct proteinopathies.
Severe proteinopathies-such as retinitis pigmentosa, a form of inherited blindness-are driven by genetic mutations that overwhelm the quality control of the post-endoplasmic reticulum (post-ER) secretory pathway, causing toxic protein accumulation. Here, we identify a therapeutic node defined by a hetero-oligomeric cargo receptor complex consisting of TMED7, 2, 9, and 10. This "entrapment complex" anchors structurally and functionally diverse mutant clients within the early secretory pathway via TMED7 binding to the integral Golgi protein GRASP55. Disruption of the entrapment complex results in the clearance of accumulated protein cargoes. In vivo ablation of the entrapment node via inducible genetic deletion or via the small molecule BRD7635 reverses histopathological hallmarks and rescues functional deficits in clinically distinct proteinopathies of the kidney and the eye, including mitigating vision loss in a mouse model of retinitis pigmentosa.
proteins
2026-08-15 | Phase I/IIa Study of an Intravitreal Optogenetic Therapy (AGN-151597) in Patients with Advanced Retinitis Pigmentosa.
Retinitis pigmentosa is an incurable, inherited retinal disease that causes vision loss and blindness. We evaluated the safety and preliminary efficacy of AGN-151597, a mutation-independent optogenetic therapy encoding channelrhodopsin-2, in patients with advanced retinitis pigmentosa. First-in-human, phase I/IIa, open-label, dose-escalation study (1 study eye/participant). Participants had advanced retinitis pigmentosa with severely impaired visual function. Participants received an intravitreal injection of low-dose (4.3 × 1010 vg/eye; n = 3), mid-dose (1.4 × 1011 vg/eye; n = 4), or high-dose (4.3 × 1011vg/eye; n = 7) AGN-151597 in the study eye. The study duration was 24 months followed by a 3-year safety extension. The primary safety endpoint was safety at 6 months as assessed by intraocular pressure and changes in visual acuity, full-field sensitivity, ambulation, and visual anatomical parameters. Efficacy measures included changes in visual acuity, full-field stimulus threshold (FST), ambulation, object detection/discrimination, visual evoked potentials, electroretinography, and visual function-related quality of life (questionnaire). Fourteen patients (median age 62 years) were enrolled. AGN-151597 treatment resulted in no clinically significant changes in ocular safety assessments. Most treatment-emergent adverse events (TEAEs) were ocular; none were severe. The most common treatment-related TEAE was transient increased intraocular pressure (n = 3). No clinically significant efficacy was observed. Full-field stimulus threshold measurements in both eyes showed good agreement between the screening and baseline visits, with coefficients of repeatability of 6.2 for blue light, 2.7 for red light, and 5.3 for white light. Overall mean FST in study eyes at baseline was -13.5 dB for blue light, -1.0 dB for red light, and -5.2 dB for white light. Participants' mean FST changed similarly in both eyes over 24 months for each light stimulus. There was no evidence of AGN-151597 efficacy in slowing vision decline in patients with advanced retinitis pigmentosa. However, the absence of safety concerns over 5 years after intravitreal administration of an adeno-associated virus type 2 vector-delivered genetic medicine is encouraging and supports further gene therapy endeavors to enhance visual function in this devastating retinal disease. Full-field stimulus threshold is a reliable test in patients with poor vision. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
2026-08-04 | WDR34 Deficiency Disrupts Retrograde Intraflagellar Transport and Induces Unfolded Protein Response-Driven Inflammation and Retinal Degeneration.
Retinitis pigmentosa (RP) is a hereditary retinal disease characterized by progressive photoreceptor cell (PRC) degeneration. WD repeat domain 34 (WDR34), an intermediate chain of dynein-2, is essential for retrograde intraflagellar transport (IFT). However, the mechanisms by which WDR34 deficiency causes retinal degeneration remain unclear. This study aims to investigate the impact of WDR34 deficiency on retrograde IFT and its contribution to retinal degeneration. WDR34 deficiency was modeled in vivo via subretinal injection of adeno-associated virus-shRNA-WDR34 and in vitro by CRISPR/Cas9-mediated knockout in 661W cells. Retinal degeneration and IFT defects were assessed by histologic, functional, and ultrastructural analyses. Proteomic analysis followed by in vivo validation was used to investigate the molecular mechanism underlying WDR34-deficient retinal degeneration. WDR34 knockdown induced progressive retinal degeneration characterized by PRC apoptosis, gradual outer nuclear layer thinning, reduced electroretinography responses, and outer segment shortening. WDR34 deficiency impaired retrograde IFT and caused rhodopsin and opsin mislocalization. These alterations induced endoplasmic reticulum stress and unfolded protein response (UPR) activation, activating the IRE1α/TRAF2/NF-κB signaling pathway, ultimately contributing to retinal inflammation and degeneration. WDR34 is crucial for maintaining retrograde IFT in PRCs. WDR34 deficiency disrupts outer segment maintenance and triggers UPR-mediated inflammatory responses and apoptosis, ultimately leading to retinal degeneration. This study reveals a novel mechanistic link among WDR34, retrograde IFT, ciliopathies, and retinal degeneration, providing potential therapeutic insights for ciliopathy-associated RP.
2026-07-27 | The Drosophila CEBPG homolog Irbp18 partners with crc (ATF4) to mediate the integrated stress response in degenerative disease models.
The integrated stress response (ISR) coordinates cellular adaptation to diverse stress conditions. In Drosophila, two bZIP transcription factors, Xrp1 and crc (ATF4 homolog), are induced during ISR. Crc protein can dimerize with two CEBP factors in vitro, but the in vivo relevance of those interactions remained unknown. Here, we report that the CEBPG homolog, Irbp18, is an essential partner of crc during ISR. Specifically, Irbp18 is broadly required for the transcriptional induction of ISR target genes in the photoreceptors of ninaEG69D, a Drosophila model of retinitis pigmentosa. Moreover, CUT&RUN analysis indicates that Irbp18 loss reduces or abolishes crc binding to target DNAs in photoreceptors and impairs crc's ability to induce target transcripts upon overexpression. Functionally, Irbp18 loss causes retinal degeneration and suppresses ISR signaling in parkin mutants, a model of Parkinson's disease. Together, these findings identify Irbp18 as a cofactor for crc, impacting pathological outcomes in Drosophila models of degeneration.
2026-05-15 | Chromophore-loaded CRALBP mutant proteins restore rod function in chromophore-deficient mice.
Visual function depends critically on the supply of visual chromophore, 11-cis-retinal, to the photoreceptor cells in the retina. Chromophore deficiency due to aging or mutations affecting its delivery and recycling in the eye by the retinal pigment epithelium (RPE) and the Müller cells cause a wide range of visual disorders. The cellular retinaldehyde-binding protein (CRALBP), expressed in both compartments, crucially aids in accelerating the recycling of visual chromophore. Here, we explored the potential of chromophore-loaded CRALBP in restoring vision in chromophore-deficient mice. We tested wild-type human CRALBP and its redox-sensitive A212C:T250C mutant, both pre-loaded with 9-cis-retinal, for their efficacy in delivering chromophore to the retina and restoring rod photoreceptor function in RPE65-deficient mice that cannot produce visual chromophore. We observed robust restoration of rod function both in the isolated retina treated with chromophore-loaded CRALBP and in vivo after a single intravitreal injection of wild-type or mutant CRALBP proteins. Notably, the recovery of rod visual function after exposure to bright light that photoactivated most of the visual pigment was greatly accelerated in CRALBP-treated RPE65-knockout mice compared to wild-type control mice. Together, our results highlight the therapeutic potential of CRALBP complexes in efficiently delivering visual chromophore to retinal rod photoreceptors.
2026-05-11 | CRUMBS-associated mutations in Retinitis Pigmentosa and its impact on molecular scaffolding.
The death of photoreceptors is a primary driver of retinal degenerative diseases, leading to irreversible vision loss. In Retinitis Pigmentosa (RP), a wide spectrum of mutations has been identified. Among these, the Crumbs (CRB) family of proteins, comprising CRB1, CRB2, and CRB3, plays a critical role in maintaining retinal homeostasis. The distribution of CRB mutations indicates population-specific variations, which may be influenced by factors such as founder effects, consanguinity, and geographic isolation. These findings suggest that genetic diagnostics and therapeutic strategies could benefit from considering population diversity. However, genotype-phenotype correlations remain complex, suggesting a modulatory role for genetic modifiers and environmental factors. Dysfunction of the CRB proteins disrupts apicobasal polarity of Retinal Pigment Epithelia (RPE) and photoreceptors, weakening their interaction and impairing phototransduction. This review highlights how mutations in conserved domains, especially the Epidermal Growth Factor (EGF)-like and Laminin G-like regions, compromise structural integrity and trigger degenerative cascades, establishing them as critical biomarkers and promising therapeutic targets for retinal degenerations.
gene therapies
2026-08-11 | Efficacy and safety of AAV RPGR gene therapy in X-linked retinitis pigmentosa: a systematic review and meta-analysis.
X-linked retinitis pigmentosa (XLRP) represents a severe inherited retinal dystrophy associated with pathogenic variants in the retinitis pigmentosa GTPase regulator (RPGR) gene. Adeno-associated virus (AAV)-mediated RPGR gene augmentation is designed to preserve photoreceptor structure and function. The purpose of this study was to critically appraise and quantitatively synthesize the efficacy and safety evidence for AAV-RPGR gene therapy in X-linked retinitis pigmentosa. Scopus, PubMed, the Cochrane Library, ScienceDirect, and Google Scholar were searched from inception through July 11, 2026. Two reviewers independently screened records, two reviewers assessed risk of bias, and extracted data were verified by a second reviewer. Proportions were synthesized using inverse-variance fixed-effect logit models with a 0.5 continuity correction for zero or all-event cells; DerSimonian-Laird random-effects models were used as sensitivity analyses. Cohort linkage, dose-stratified safety, and overlap-adjusted analyses were performed. The search identified 571 records and included 12 clinical reports. Pooled retinal sensitivity improvement was 73.8% (95% confidence interval, 56.0%-86.1%; 25/33 participants), and pooled visual function improvement was 52.3% (95% confidence interval, 38.0%-66.2%; 28/52 participants). The pooled adverse-event proportion was 42.6% (95% confidence interval, 27.2%-59.5%; 42/90 participants), intraocular inflammation was 45.5% (95% confidence interval, 34.6%-56.8%; 36/81 participants), and intraocular-pressure elevation was 34.9% (95% confidence interval, 24.2%-47.4%; 22/63 participants). Product-specific dose analyses showed greater inflammatory or ocular serious adverse-event frequencies at higher vector exposure. AAV-RPGR gene therapy demonstrates clinically relevant functional signals across multiple outcome domains with a structured and monitorable ocular safety profile. Cohort-linked synthesis, dose-specific interpretation, standardized outcome definitions, and long-term multinational follow-up provide a rigorous framework for subsequent clinical development.
2026-08-10 | Defining a Novel RPGR Phenotype of Sector Retinitis Pigmentosa With Cone Dystrophy.
RPGRORF15-associated retinal degeneration is characterized by clinical and genetic heterogeneity: Proximal mutations typically result in rod-cone dystrophy, distal mutations in cone-dominated disease, and mutations within open-reading frame 15 (ORF15) in either phenotype. This study characterizes an intermediate phenotype in which patients exhibit a combination of cone dystrophy and incomplete (sectoral) rod-cone dystrophy associated with mutations in the ORF15 region and explores potential mechanistic explanations. A multinational, multicenter, observational, cross-sectional case series was conducted using databases from RPGR-related retinal dystrophy clinical trial referral centers. Patients with molecularly confirmed RPGR-related cone dystrophy or RPGR-related cone-rod dystrophy were studied. Individuals exhibiting a mixed phenotype of cone dystrophy and sectoral retinitis pigmentosa were identified. In silico analyses assessed the impact of identified mutations on RPGR transcript expression and protein structure. Fourteen patients exhibited a cone dystrophy phenotype with bilateral, symmetrical regions of outer retinal atrophy distributed along the inferior vascular arcades and extending nasally. All harbored ORF15 mutations within a defined transitional zone. All of the mutations were predicted to produce truncated proteins with partial or complete loss of function. Additionally, several were predicted to disrupt splicing regulatory elements. An intermediate phenotype consisting of a cone dystrophy with sectoral retinitis pigmentosa development was characterized. These patients may benefit from full-length RPGR gene therapy. Furthermore, we demonstrate that this rare presentation closely resembles the phenotype observed in some patients with loss-of-function TTLL5-associated cone dystrophy with sectoral involvement.
2026-08-07 | CDHR1-associated retinal degeneration: Clinical phenotypes and therapeutic approaches.
CDHR1 is a recently identified cause of autosomal recessive retinal degeneration manifesting as three distinct clinical phenotypes: macular dystrophy, cone-rod dystrophy or retinitis pigmentosa. In this review, we summarise the discovery and characterisation of CDHR1, clinical phenotypes, natural history and therapeutic approaches including gene supplementation and CRISPR gene editing. CDHR1 is a non-classical cadherin that is highly expressed in cone and rod photoreceptors and is essential for the higher-order organisation of the functionally critical outer segments. Promising pre-clinical data show that AAV gene supplementation therapy delivered by subretinal injection can lead to long-term morphological, structural, functional and behavioural improvements in the Cdhr1 knockout mouse model. Notably, CDHR1 supplementation restored full-length photoreceptor outer segments that are usually shortened and disorganised in disease models and prolonged photoreceptor survival - key mechanisms for the functional and behavioural rescue effects that were observed. The disease is likely to be underdiagnosed because CDHR1-associated macular dystrophy - likely to be the most common disease phenotype - is most often caused by a 'silent' nucleotide substitution that has previously been overlooked by genetic testing. Since the macular dystrophy phenotype has phenotypic similarities to advanced dry age-related macular degeneration (AMD), misdiagnoses are common. CDHR1-associated macular dystrophy also shares phenotypic features with a variety of monogenic masquerades such as ABCA4, PRPH2 and GUCY2D-associated macular dystrophies; we present a flowchart to guide the clinical distinction of these disorders which is now critical for patients as their treatments diverge. AAV gene therapy may be beneficial across the CDHR1 disease spectrum - including those with hypomorphic variants associated with macular dystrophy or retinitis pigmentosa. The coding sequence fits into AAV and with the macular dystrophy phenotype, there is a large time window for potential intervention and a large treatable population. Hence clinical trials are anticipated. It is therefore important that patients with CDHR1-associated retinal degeneration are accurately phenotyped and genetically confirmed to support the application of CDHR1 gene therapy.
2026-08-03 | Identification of a Duplication in the RP17 Locus in an Individual With Pathogenic CEP290 Variants: Implications for RP17 Variant Classification.
To assess the pathogenicity of a novel duplication in the RP17 locus identified in a cone dystrophy proband with biallelic CEP290 variants. Structural variants (SVs) in this locus have previously been associated with dominant retinitis pigmentosa. Inheritance of the duplication was assessed by breakpoint polymerase chain reaction (PCR). Ophthalmic evaluation included fundus examination, multimodal retinal imaging, and full-field electroretinogram (ERG). A proband-derived pluripotent stem cell line was differentiated into photoreceptor precursor cells (PPCs) and retinal organoids (ROs). Variant-induced mis-splicing of CEP290 was assessed by reverse-transcription PCR (RT-PCR) and long-read cDNA sequencing, and immunohistochemistry was used to assess photoreceptor morphology. Expression of GDPD1 was quantified by quantitative RT-PCR. The proband and father carried the 324-kb duplication in the RP17 locus. The father was clinically unaffected, but the proband showed features of cone dystrophy, including reduced visual acuity, foveal abnormalities, diminished cone density, and preserved dark-adapted but absent light-adapted ERG responses. The compound heterozygous variants in CEP290 resulted in pseudoexon inclusion and exon 36 skipping in patient-derived retinal cells. Immunohistochemistry revealed altered ciliation and reduced trafficking of L/M opsin and rhodopsin in ROs. In silico modeling predicted that the novel RP17 duplication does not disrupt chromatin looping, and GDPD1 expression was not upregulated in patient ROs, in contrast to pathogenic RP17-SVs. The cone dystrophy phenotype of the proband can be attributed to the CEP290 variants, whereas the novel RP17 duplication can be classified as likely benign based on the integrated evidence. These findings emphasize the importance of modeling and functional studies for accurately classifying RP17-SVs and preventing misinterpretation in clinical diagnostics.
2026-07-15 | Cone-Rod Dystrophy PCARE-Associated Retinopathy.
Background and Clinical Significance: Biallelic pathogenic variants in the PCARE gene (photoreceptor cilium actin regulator), also known as C2orf71 (chromosome 2 open reading frame 71), are typically associated with retinitis pigmentosa type 54 (RP54) and, less frequently, with cone-rod dystrophy (CORD23). Case Presentation: A 52-year-old man presented with an eight-year history of progressive visual loss, without photophobia or nyctalopia. He underwent a comprehensive ophthalmological evaluation, including multimodal retinal imaging, automated perimetry, and full electrophysiological testing, in accordance with International Society for Clinical Electrophysiology of Vision (ISCEV)'s standards. Genetic testing was performed using next-generation sequencing (NGS) with an inherited retinal dystrophy gene panel, and findings were confirmed by Sanger sequencing. Clinical examination revealed bilateral macular atrophy with minimal foveal sparing and a central scotoma. Optical coherence tomography (OCT) showed disruption of the outer retinal layers and retinal pigment epithelium (RPE) abnormalities. Fundus autofluorescence (FAF) demonstrated central hypoautofluorescence surrounded by a hyperautofluorescent ring. Electrophysiological testing revealed severely reduced rod- and cone- mediated responses on full-field electroretinography (ERG), absent pattern ERG responses, and markedly reduced multifocal ERG responses, indicating widespread retinal dysfunction with significant macular involvement. Genetic analysis identified a homozygous pathogenic nonsense variant in PCARE [c.3289C>T; p.(Gln1097*)], confirming the diagnosis of an autosomal recessive inherited retinal dystrophy. Conclusions: Biallelic PCARE variants can cause late-onset severe retinal dystrophy, with predominant macular involvement and cone-rod dysfunction. Given its phenotypic overlap with other inherited retinal diseases, accurate diagnosis requires the integration of multimodal retinal imaging, electrophysiological testing, and comprehensive genetic analysis.
cell therapies
2026-07-09 | Photoreceptor-targeted engineered exosomes encapsulating black phosphorus quantum dots for alleviating photoreceptor degeneration.
Photoreceptor degeneration is a major cause of irreversible visual impairment worldwide, most notably in retinitis pigmentosa (RP). Here, we developed a dual-targeted therapeutic nanoplatform by loading black phosphorus quantum dots (BPQDs) into human dental pulp mesenchymal stem cell-derived exosomes (hDPSC-Exos) and surface-modifying with cell-penetrating peptide transactivated transcription (TAT) and photoreceptor-specific peptide MH42, namely TAT/MH42-engineered black phosphorus quantum dot-loaded exosomes (M/T-BPQD@Exos). M/T-BPQD@Exos showed typical exosomal morphology and good uniformity. In vitro, M/T-BPQD@Exos effectively protected 661 W photoreceptor cells against N-methyl-N-nitrosourea (MNU) injury. In vivo, M/T-BPQD@Exos specifically accumulated in the outer nuclear layer (ONL) and significantly preserved retinal structure and visual function in MNU-induced photoreceptor degeneration rats. Biosafety assessment confirmed no obvious systemic toxicity and inflammation. Mechanistically, M/T-BPQD@Exos alleviated calcium overload, maintained mitochondrial integrity, and suppressed mitochondrial apoptosis by regulating Bcl-2, Bax, and cleaved caspase-3. This study provides a safe and precise strategy for photoreceptor protection in retinal degenerative diseases.
2026-05-31 | Stem cell therapy in retinal disease.
Stem cell therapy presents a new solution to cure degenerative diseases of the retina, which normally have limited ability to regenerate after injury. Stem cells are cells capable of self-renewal and differentiation into more specialized cells, and can be derived from both embryonic and adult sources. This definition encompasses a heterogeneous group of cells possessing varied potency and characteristics. Current attempts in applying stem cell technology to the retina have primarily focused on regenerating the retinal pigment epithelium (RPE) and light-sensing photoreceptor cells. They have not only shown the ability to prevent the death of host photoreceptors, but they can also differentiate into all major retinal cell types to replace lost cells. In vivo experiments, primarily performed in mice, have found that stem cell-derived RPE cells, photoreceptors, and their precursors can survive long-term in animal models without tumorigenicity or immune rejection. Following transplantation, these cells were able to integrate and mature in vivo, forming synapse-like structures with host retinal cells. Furthermore, transplants in mice were able to rescue visual function at a cellular and behavioral level. These promising preclinical results have led to clinical trials testing cell therapy in numerous diseases, including Stargardt macular dystrophy, age-related macular degeneration, retinitis pigmentosa, and central retinal vein occlusion. These trials have demonstrated the safety of cell therapy and have improved visual function in some patients. Scientific advances in the culturing of retinal organoids and the understanding of cell redifferentiation are informing the development of better stem cell therapies, which hold great potential for restoring vision to patients with retinal dystrophies.
2026-05-27 | Subtenon Autologous Platelet-Rich Plasma in Degenerative Retinal Diseases: A Prospective Pilot Study of Safety and Exploratory Functional Signals in Retinitis Pigmentosa and EMAP.
Purpose: To evaluate the safety and feasibility of repeated subtenon administration of autologous platelet-rich plasma (PRP) in patients with degenerative retinal diseases and to explore preliminary, hypothesis-generating functional observations in retinitis pigmentosa (RP) and extensive macular atrophy with pseudodrusen-like appearance (EMAP). Methods: This prospective, open-label, uncontrolled pilot study included 13 patients (6 RP, 7 EMAP) who received three subtenon PRP injections (1.5 mL each) at baseline, Month 2, and Month 4, with follow-up through Month 6. The study was designed primarily to assess safety and feasibility and was not powered or intended to evaluate efficacy. The primary outcome was safety, including adverse events and intraocular pressure changes. Exploratory secondary outcomes included best-corrected visual acuity (BCVA, logMAR), visual field mean deviation (MD), and structural optical coherence tomography (OCT) parameters. Electrophysiological outcomes were analyzed descriptively due to incomplete paired data. Analyses were conducted within diagnostic groups, and no between-group comparisons were performed. Results: All 13 patients completed the study. No serious adverse events or permanent ocular morbidity were observed. Two transient and self-limited adverse events occurred (anterior uveitis and intraocular pressure elevation), both resolving without sequelae. In the overall cohort, BCVA remained stable without statistically significant change. In the RP subgroup, a small exploratory change in BCVA was observed (mean ΔlogMAR -0.09; nominal p = 0.048), corresponding to approximately 4-5 ETDRS letters; however, this finding was associated with wide confidence intervals and limited statistical power and should be interpreted cautiously. In the EMAP subgroup, functional stability was observed without evidence of consistent improvement. Visual field mean deviation and OCT findings were consistent with absence of short-term deterioration across available paired data. Electrophysiological outcomes showed no consistent directional change. Conclusions: Repeated subtenon PRP administration appeared feasible and well tolerated in this small, uncontrolled pilot cohort. Any observed functional changes are preliminary and hypothesis-generating only and do not establish efficacy. Larger, adequately powered controlled studies with standardized endpoints are required to determine the potential role of PRP in degenerative retinal diseases.
2026-05-15 | Inhibitory Circuits Can Restore OFF Pathway Responses in Retinal Prostheses.
One of the first steps in processing visual information is to split the light signal captured by photoreceptors into complementary ON and OFF pathways, which separately encode increases and decreases in luminance. In blind patients with retinal degeneration, optoelectronic prostheses can successfully activate the ON pathway and evoke bright percepts; however, patients do not perceive dark features. This indicates that the OFF pathway is not being activated by existing prosthetics. To quantify OFF pathway deficits, we stimulated retinal ganglion cells (RGCs) in a mouse model of retinitis pigmentosa of either sex with electrical stimulation mimicking retinal prosthetic activation and recorded their voltage responses using whole-cell recording. We found that most OFF RGCs respond with incorrect ON responses, except for one specific subtype of RGC, the OFFα, which retained correct OFF-type responses following the termination of stimulation. We found that these preserved OFF responses were driven by postinhibitory rebound excitation, mediated by hyperpolarization-activated cyclic nucleotide-gated channels. Using a combinatorial genetic approach to achieve chemogenetic control, we identified AII amacrine cells as the presynaptic source driving these electrically evoked OFF responses. These insights into how the OFF pathway responds to artificial stimulation suggest new opportunities to improve prosthetic vision restoration through tuning of stimulation parameters.
2026-05-03 | Retinal organoids: current status of development and new avenues for application in disease modeling, drug discovery and therapeutics.
Visual impairment affects over 2.2 billion people worldwide and the major causes include age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. For research in these areas, although animal models offer a more physiologically complex system than in vitro approaches, their use raises ethical considerations, and species-specific differences such as variations in protein sequences and signaling pathways. This can limit the direct translatability of the outcomes. Traditional 2-D cell cultures, in contrast, lack the multicellular organization and dynamic microenvironment necessary to replicate human retinal complexity. Retinal organoids (ROs), three-dimensional tissue constructs derived from pluripotent stem cells, have emerged as a promising model due to their human origin and complex cellular interactions that cannot be achieved in conventional 2-D/3-D co-culture models. In this review, we provide a brief overview of the evolution from 2-D to 3-D retinal models, highlight the structural and functional features of ROs including the presence of layered retinal architecture, photoreceptor outer segment formation, and light-responsive electrophysiological activity and summarize their applications in disease modeling, drug discovery, and gene and cell therapy. ROs represent a significant advancement over traditional models by enabling the recapitulation of human-specific retinal development, facilitating the study of patient-derived disease phenotypes, and providing a platform for personalized therapeutic screening. Their development has deepened understanding of pathological mechanisms in conditions such as retinitis pigmentosa and AMD, while enabling preclinical testing of targeted interventions like CRISPR-based gene editing and photoreceptor cell replacement. Nonetheless, challenges remain in fully replicating retinal vascularization, long-term functional maturation, and synaptic connectivity, underscoring the need for continued refinement and integration with complementary model systems.
other
2026-07-24 | DNAJC17 deficiency: A novel inborn error of immunity with TNF-driven autoinflammation.
Inborn Errors of Immunity (IEI) encompass a broad spectrum of monogenic disorders with variable clinical presentations, including recurrent infections, autoimmunity, and systemic inflammation. Loss-of-function mutations in DNAJC17 have been previously linked to retinal dystrophy and hypogammaglobulinemia; however, the complete immunological phenotype and underlying autoinflammatory mechanisms remain poorly characterized. We conducted a comprehensive clinical, molecular, and immunological investigation of three affected individuals from two unrelated consanguineous families. Our evaluation included whole genome sequencing with systematic exclusion of alternative genetic etiologies, quantitative analysis of DNAJC17 mRNA expression, and assessment of intracellular DNAJC17 protein levels. In addition, we performed in-depth immunophenotyping of adaptive and innate immune cell subsets, cytokine profiling, and interferon-stimulated gene expression analysis, alongside longitudinal evaluation of responses to therapeutic interventions. All three patients presented with early-onset retinitis pigmentosa, recurrent fever, lymphadenitis, and hypogammaglobulinemia. Sanger sequencing confirmed a homozygous variant (c.681G>A; p.Ala227=) in DNAJC17 resulting in exon 9 skipping. Comprehensive whole genome analysis excluded pathogenic variants in other immune-related genes. Quantitative RT-PCR demonstrated reduced DNAJC17 mRNA levels and flow cytometry showed decreased intracellular protein levels, consistent with a hypomorphic loss-of-function effect. Immunological evaluation revealed distinct abnormalities in T, B, and NK-cell subsets, with altered monocyte and dendritic cell populations indicating innate and adaptive immune dysregulation. Inflammatory profiling identified increased cytokine activity, including TNF-α and IL-6, alongside mild induction of interferon-stimulated genes. Conventional immunomodulatory therapies failed to achieve sustained remission. In contrast, TNF inhibitor therapy resulted in dramatic clinical improvement with normalization of inflammatory markers, sustained for over three years without significant adverse events. Our findings establish DNAJC17 deficiency as a novel monogenic inborn error of immunity characterized by retinopathy, combined immunodeficiency, and TNF-driven autoinflammation responsive to targeted TNF blockade. The underlying immune abnormalities underscore the essential role of DNAJC17 in maintaining immune homeostasis and mitochondrial function. This work provides mechanistic insights into disease pathogenesis and establishes a rational, precision medicine therapeutic approach for this newly defined syndrome.
2026-06-11 | Multimodal imaging and intravitreal faricimab for polypoidal choroidal vasculopathy associated with a choroidal nevus in genetically confirmed Usher syndrome type 2: a case report.
Usher syndrome is an autosomal recessive disorder characterized by retinitis pigmentosa (RP), sensorineural hearing loss, and vestibular dysfunction. Polypoidal choroidal vasculopathy (PCV) is characterized by branching neovascular networks and polypoidal lesions. While typically classified within the pachychoroid spectrum, PCV can also manifest in eyes without choroidal thickening. Conversely, RP is usually associated with choroidal thinning, which may lead to underdiagnosis of PCV. To the best of our knowledge, PCV has not previously been reported in patients with Usher syndrome. Here, we present the first genetically confirmed case of Usher syndrome type 2 complicated by PCV that was successfully managed with intravitreal faricimab. A 63-year-old man presented with night blindness. The diagnosis of Usher syndrome type 2 was confirmed based on bilateral RP features, moderate sensorineural hearing loss, and two pathogenic USH2A variants. Six years after the initial diagnosis, the patient developed visual disturbance in the left eye, with the best-corrected visual acuity (BCVA) declining to 20/80. Multimodal imaging, including spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography angiography, confirmed the diagnosis of PCV. An amelanotic choroidal nevus was also identified on SD-OCT. After five intravitreal faricimab injections, the BCVA improved to 20/30, with a 75% reduction in pigment epithelial detachment height and complete subretinal fluid resolution without adverse effects. To our knowledge, this is the first reported case of PCV associated with a choroidal nevus in a patient with genetically confirmed Usher syndrome type 2. PCV should not be excluded in patients with RP despite characteristic choroidal thinning. Intravitreal faricimab was effective and well-tolerated, suggesting its therapeutic potential in such cases.
2026-06-04 | Targeted antisense oligonucleotide therapy rescues PRPF31 expression in retinitis pigmentosa caused by a splicing mutation.
Pathogenic variants in splicing factors are the second most common cause of autosomal dominant retinitis pigmentosa, with mutations in PRPF31 being the most prevalent. Here, we characterize a novel intronic variant in PRPF31 (c.1074-11C>G) that creates a cryptic 3' splice site, resulting in an aberrantly spliced transcript predicted to encode a protein with an altered C terminus. However, the pathogenic protein is unstable and undetectable in patient-derived induced pluripotent stem cells (iPSCs). In addition, expression of the full-length PRPF31 protein was reduced in patient-derived retinal pigment epithelium (RPE). To correct the splicing defect, we designed a panel of antisense oligonucleotides (ASOs) targeting putative RNA-binding sites in exon 10 and intron 10 and identified a candidate that corrects PRPF31 splicing in a minigene reporter system as well as in patient-derived iPSCs and RPE. We further showed that ASO treatment enhances PRPF31 protein expression in patient-derived iPSC and RPE carrying the intronic mutation, supporting the potential of the ASO-based approach to restore PRPF31 expression in patients with the same or similar splicing defects.
2026-05-27 | TPM1 drives cytoskeleton-immunometabolism coupling and LGALS9/CD45-mediated neuroinflammatory propagation in retinitis pigmentosa.
Retinitis pigmentosa (RP), the most prevalent inherited retinal degeneration, features progressive photoreceptor loss with no approved disease-modifying therapies. While microglia-driven neuroinflammation accelerates RP progression, its sustaining mechanisms remain elusive. Through integrated multiomics profiling of retinal degeneration 10 (rd10) mice, we identify tropomyosin 1 (TPM1) as a previously unrecognized cytoskeletal-immune regulator orchestrating spatial neuroinflammation in RP. Genetic ablation of Tpm1 attenuated microglial reactivity and preserved vision, whereas overexpression triggered self-reinforcing inflammation via four interlocked axes: (i) TPM1-mediated activator protein-1 (AP-1) hyperactivation initiates senescence-associated secretory phenotype (SASP) through mitogen-activated protein kinase (MAPK) kinase/extracellular signal-regulated kinase 3-dependent MAPK signaling; (ii) SASP subsequently mediates reduced phagocytosis; (iii) Tpm1-Apoe/Fabp5 axis disruption precipitates lipid droplet accumulation with cholesterol crystallization; (iv) galectin-9 (LGALS9)/CD45-mediated intermicroglial signaling propagates inflammatory signals across the retina. Our work redefines TPM1 as a linchpin in self-sustaining neurodegeneration cycles, where cytoskeletal dysfunction fuels immunometabolic collapse. These findings unveil precision therapeutic strategies targeting TPM1 hubs-notably the LGALS9/CD45 axis-to disrupt inflammatory cycles while preserving retinal homeostasis.
2026-05-20 | Intravitreal Adalimumab in Retinitis Pigmentosa: A Prospective Pilot Study Assessing Ocular Safety and Feasibility.
Objective The objective of this study was to evaluate the short-term ocular safety, feasibility, and exploratory functional signals associated with intravitreal adalimumab (ADA) in patients with retinitis pigmentosa (RP). Methods This prospective, single-arm pilot study included 21 patients with RP who received intravitreal adalimumab (2 mg/0.05 mL) at baseline, month 2, and month 4, with follow-up to month 6. The primary objective was to assess ocular safety and treatment feasibility. Exploratory functional outcomes included best-corrected visual acuity (BCVA, logarithm of the minimum angle of resolution (LogMAR)) and automated perimetry parameters (mean deviation (MD), pattern standard deviation (PSD), and Field Preservation Deviation Index (FPDI)). Structural assessment was performed using optical coherence tomography (OCT). Analyses compared baseline and month 6 outcomes using paired statistical methods. BCVA values were analyzed at the patient level as the mean of both eyes. Results All scheduled intravitreal injections were successfully completed, and no serious ocular adverse events were observed during follow-up. Mean BCVA showed no statistically significant change from baseline to month 6 (0.76 to 0.70 LogMAR; p = 0.115). Visual field parameters (MD, PSD, and FPDI) remained stable, with no statistically significant differences over time. OCT findings demonstrated advanced baseline structural alterations consistent with RP, without evidence of treatment-related anatomical deterioration or cystoid macular edema during follow-up. Flicker electroretinography (ERG) responses were measurable in a limited subset of patients and were analyzed descriptively, showing no consistent evidence of decline. Conclusions In this prospective pilot study, intravitreal adalimumab demonstrated a favorable short-term ocular safety profile and was feasible to administer in patients with retinitis pigmentosa. No significant functional or structural changes were observed over six months. These findings are hypothesis-generating and support the need for controlled studies to further evaluate the safety and potential role of tumor necrosis factor alpha (TNF-α) inhibition in inherited retinal degeneration.
small molecules
2026-08-13 | N-acetylcysteine suppresses retinal defects in Drosophila models of SNRNP200-associated retinitis pigmentosa.
Retinitis Pigmentosa (RP) is an inherited retinal degenerative disease that affects 1 in 4000 individuals worldwide and can lead to complete blindness. Early stages of RP involve death of rod photoreceptors via apoptosis, causing loss of peripheral and night vision, which is followed by death of cone photoreceptors, leading to loss of central and daytime vision. Mutations in over 300 genes cause RP. Many of these genes encode retina-specific proteins; however, some encode globally expressed proteins, such as pre-mRNA splicing factors. This study is focused on mutations in the SNRNP200 gene encoding a core pre-mRNA splicing factor. The pathological mechanisms of SNRNP200-associated RP are not well understood and treatments are limited. An approach to study pathogenic mechanisms is to utilize model organisms. Therefore, we developed Drosophila models in which RP-causing mutations were introduced into the Drosophila melanogaster orthologue Snrnp200. In addition, we used RNAi to knock-down Snrnp200 in the developing eye. Depletion of Snrnp200 caused an adult rough eye phenotype due to apoptosis of cells in the retina. When human RP-causing mutations were modeled in Drosophila Snrnp200, they resulted in abnormal retinal electrophysiology and defective patterning of photoreceptors. Further analysis of the photoreceptors revealed mitochondrial defects and altered expression of genes related to redox homeostasis. Consistent with these changes, treatment with the antioxidant N-acetylcysteine (NAC) partially suppressed the photoreceptor defects. Taken together, these findings established a new genetic model for studies of splicing-factor associated RP that recapitulates aspects of the human disease and suggests that antioxidants might serve as a treatment for individuals with SNRNP200-associated RP.
2026-08-10 | The efficacy and safety of oral and topical carbonic anhydrase inhibitors for the treatment of macular edema secondary to retinitis pigmentosa: a systematic review and meta-analysis.
Carbonic anhydrase inhibitors (CAIs) are commonly used to treat macular edema (ME) secondary to retinitis pigmentosa (RP). This meta-analysis aims to better understand the efficacy of topical or oral CAIs therapy and to summarize the rates of improvement and recurrence of ME, as well as adverse events. A systematic review was conducted by searching PubMed, Web of Science, Embase, CENTRAL, CNKI, Wanfang, and VIP databases with no language filters applied. Eligible studies were those investigating topical or oral CAIs for the treatment of ME secondary to RP. Central macular thickness (CMT) and best-corrected visual acuity (BCVA) were extracted as the primary outcome measures for comprehensive analysis. This meta-analysis identified a total of 16 eligible studies, encompassing 267 patients (487 eyes). Moderate certainty evidence from RCTs demonstrated that oral CAIs significantly improved BCVA, whereas topical CAIs showed no statistically significant effect. Low to moderate certainty evidence from non-RCTs revealed that both oral and topical CAIs significantly improved CMT (both P < 0.001). This meta-analysis indicates that oral CAI therapy significantly reduces CMT and improves BCVA in patients with RP, whereas the effect of topical CAIs on BCVA remains uncertain. A large-scale, prospective randomized controlled trial would be ideal to further investigate the differences in clinical efficacy and adverse events between oral and topical CAIs in this patient population.
2026-07-30 | Gap junctions form bridges between bench studies and clinical ophthalmology.
In retinal neurodegenerative disorders, the initial degeneration of primary target cells is frequently followed by a phenomenon known as the bystander effect, wherein neighboring, initially unaffected cells also undergo degeneration. This secondary cell death can exceed the number of directly insulted cells (Frantseva et al., 2002a,b; de Rivero Vaccari et al. 2007; Wang et al. 2010; Park et al. 2011; Akopian et al. 2014; O'Brien and Bloomfield, 2018). Although the precise mechanisms underlying the bystander effect remain incompletely understood, gap junctions (GJs) have been implicated in mediating the spread of pro-death signals from injured to adjacent cells. Consequently, GJs have become a focal point in recent research, with GJ blockade proposed as a neuroprotective strategy in progressive retinal diseases, such as diabetic retinopathy, ischemia, and glaucoma. However, GJs are essential in physiological neuronal communication, and their prolonged inhibition may disrupt visual processing (Bloomfield and Völgyi, 2009; Völgyi et al., 2013; O'Brien and Bloomfield, 2018), thereby limiting the therapeutic utility of GJ blockades in the treatment of chronic retinal conditions. Considering this, we propose an alternative hypothesis: rather than solely contributing to neurodegeneration, GJs may also support cell survival by facilitating the intercellular transmission of protective molecules (termed here as 'health-signals') that counteract apoptotic cascades and possibly attenuate the primary insult itself. In this framework, GJs could disseminate "health signals" across the retinal network, suggesting that co-administering neuroprotective agents with GJ permeability enhancers might amplify their therapeutic reach. While this hypothesis assumes that key endogenous molecules can cross GJs, their specific properties and transjunctional dynamics remain poorly understood. This review consolidates current knowledge on GJ-mediated communication and explores its clinical utility in retinal neuroprotection.
2026-07-29 | Metabolomics Effects of Folding Correction in Retinitis Pigmentosa Rhodopsin Mutant P23A.
Retinitis pigmentosa (RP) is a hereditary retinal degeneration disorder often caused by mutations in the rhodopsin gene, leading to photoreceptor death and vision loss. While structural misfolding of rhodopsin is a known contributor to disease pathology, the mechanisms of its cellular and in particular metabolic consequences are poorly understood. To study the direct effects of rhodopsin misfolding and structural rescue on cellular metabolism, we used the P23A mutant and its N2C/D282C stabilized counterpart as a structural tool to assess how differences in folding stability relate to measurable changes at the metabolite level. The engineered cysteine pair allows the formation of a disulfide bond restoring structural integrity and reinforcing the stable seven-transmembrane bundle. We used untargeted Gas Chromatography-Mass Spectrometry (GC-MS) metabolomics analysis conducted in inducible rhodopsin-expressing cell lines, providing a broad and general profiling of metabolic pathway alterations in response to the expression of RP mutants and their structurally rescued counterparts. Principal component analysis, hierarchical clustering, and K-means clustering revealed distinct metabolic signatures associated with each rhodopsin-expressing cell line, demonstrating a highly significant effect of genotype on global metabolite composition (F = 71.679; R2 = 0.93724; p = 0.001). Pairwise comparisons and background-subtracted analyses identified consistent alterations in arginine and proline metabolism, glutathione metabolism, and the TCA cycle, nucleotide, amino acid metabolism, redox regulation, and mitochondrial function in cells expressing misfolded P23A. Pathway enrichment highlighted key metabolites in the respective pathways as candidate biomarkers for the rhodopsin P23A mutation. As this study employs a non-retinal cell system, the observed metabolic changes reflect conserved responses to rhodopsin misfolding and proteostatic stress in the ER rather than a direct model of rod cell degeneration. Our findings support the hypothesis that there is a biochemical link, most likely the UPR, between rhodopsin folding/misfolding status and metabolic homeostasis and suggest that targeted metabolic modulation may offer a complementary therapeutic avenue for treating RP.
2026-07-29 | A cargo receptor entrapment complex is a therapeutic node for genetically and clinically distinct proteinopathies.
Severe proteinopathies-such as retinitis pigmentosa, a form of inherited blindness-are driven by genetic mutations that overwhelm the quality control of the post-endoplasmic reticulum (post-ER) secretory pathway, causing toxic protein accumulation. Here, we identify a therapeutic node defined by a hetero-oligomeric cargo receptor complex consisting of TMED7, 2, 9, and 10. This "entrapment complex" anchors structurally and functionally diverse mutant clients within the early secretory pathway via TMED7 binding to the integral Golgi protein GRASP55. Disruption of the entrapment complex results in the clearance of accumulated protein cargoes. In vivo ablation of the entrapment node via inducible genetic deletion or via the small molecule BRD7635 reverses histopathological hallmarks and rescues functional deficits in clinically distinct proteinopathies of the kidney and the eye, including mitigating vision loss in a mouse model of retinitis pigmentosa.
proteins
2026-08-15 | Phase I/IIa Study of an Intravitreal Optogenetic Therapy (AGN-151597) in Patients with Advanced Retinitis Pigmentosa.
Retinitis pigmentosa is an incurable, inherited retinal disease that causes vision loss and blindness. We evaluated the safety and preliminary efficacy of AGN-151597, a mutation-independent optogenetic therapy encoding channelrhodopsin-2, in patients with advanced retinitis pigmentosa. First-in-human, phase I/IIa, open-label, dose-escalation study (1 study eye/participant). Participants had advanced retinitis pigmentosa with severely impaired visual function. Participants received an intravitreal injection of low-dose (4.3 × 1010 vg/eye; n = 3), mid-dose (1.4 × 1011 vg/eye; n = 4), or high-dose (4.3 × 1011vg/eye; n = 7) AGN-151597 in the study eye. The study duration was 24 months followed by a 3-year safety extension. The primary safety endpoint was safety at 6 months as assessed by intraocular pressure and changes in visual acuity, full-field sensitivity, ambulation, and visual anatomical parameters. Efficacy measures included changes in visual acuity, full-field stimulus threshold (FST), ambulation, object detection/discrimination, visual evoked potentials, electroretinography, and visual function-related quality of life (questionnaire). Fourteen patients (median age 62 years) were enrolled. AGN-151597 treatment resulted in no clinically significant changes in ocular safety assessments. Most treatment-emergent adverse events (TEAEs) were ocular; none were severe. The most common treatment-related TEAE was transient increased intraocular pressure (n = 3). No clinically significant efficacy was observed. Full-field stimulus threshold measurements in both eyes showed good agreement between the screening and baseline visits, with coefficients of repeatability of 6.2 for blue light, 2.7 for red light, and 5.3 for white light. Overall mean FST in study eyes at baseline was -13.5 dB for blue light, -1.0 dB for red light, and -5.2 dB for white light. Participants' mean FST changed similarly in both eyes over 24 months for each light stimulus. There was no evidence of AGN-151597 efficacy in slowing vision decline in patients with advanced retinitis pigmentosa. However, the absence of safety concerns over 5 years after intravitreal administration of an adeno-associated virus type 2 vector-delivered genetic medicine is encouraging and supports further gene therapy endeavors to enhance visual function in this devastating retinal disease. Full-field stimulus threshold is a reliable test in patients with poor vision. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
2026-08-04 | WDR34 Deficiency Disrupts Retrograde Intraflagellar Transport and Induces Unfolded Protein Response-Driven Inflammation and Retinal Degeneration.
Retinitis pigmentosa (RP) is a hereditary retinal disease characterized by progressive photoreceptor cell (PRC) degeneration. WD repeat domain 34 (WDR34), an intermediate chain of dynein-2, is essential for retrograde intraflagellar transport (IFT). However, the mechanisms by which WDR34 deficiency causes retinal degeneration remain unclear. This study aims to investigate the impact of WDR34 deficiency on retrograde IFT and its contribution to retinal degeneration. WDR34 deficiency was modeled in vivo via subretinal injection of adeno-associated virus-shRNA-WDR34 and in vitro by CRISPR/Cas9-mediated knockout in 661W cells. Retinal degeneration and IFT defects were assessed by histologic, functional, and ultrastructural analyses. Proteomic analysis followed by in vivo validation was used to investigate the molecular mechanism underlying WDR34-deficient retinal degeneration. WDR34 knockdown induced progressive retinal degeneration characterized by PRC apoptosis, gradual outer nuclear layer thinning, reduced electroretinography responses, and outer segment shortening. WDR34 deficiency impaired retrograde IFT and caused rhodopsin and opsin mislocalization. These alterations induced endoplasmic reticulum stress and unfolded protein response (UPR) activation, activating the IRE1α/TRAF2/NF-κB signaling pathway, ultimately contributing to retinal inflammation and degeneration. WDR34 is crucial for maintaining retrograde IFT in PRCs. WDR34 deficiency disrupts outer segment maintenance and triggers UPR-mediated inflammatory responses and apoptosis, ultimately leading to retinal degeneration. This study reveals a novel mechanistic link among WDR34, retrograde IFT, ciliopathies, and retinal degeneration, providing potential therapeutic insights for ciliopathy-associated RP.
2026-07-27 | The Drosophila CEBPG homolog Irbp18 partners with crc (ATF4) to mediate the integrated stress response in degenerative disease models.
The integrated stress response (ISR) coordinates cellular adaptation to diverse stress conditions. In Drosophila, two bZIP transcription factors, Xrp1 and crc (ATF4 homolog), are induced during ISR. Crc protein can dimerize with two CEBP factors in vitro, but the in vivo relevance of those interactions remained unknown. Here, we report that the CEBPG homolog, Irbp18, is an essential partner of crc during ISR. Specifically, Irbp18 is broadly required for the transcriptional induction of ISR target genes in the photoreceptors of ninaEG69D, a Drosophila model of retinitis pigmentosa. Moreover, CUT&RUN analysis indicates that Irbp18 loss reduces or abolishes crc binding to target DNAs in photoreceptors and impairs crc's ability to induce target transcripts upon overexpression. Functionally, Irbp18 loss causes retinal degeneration and suppresses ISR signaling in parkin mutants, a model of Parkinson's disease. Together, these findings identify Irbp18 as a cofactor for crc, impacting pathological outcomes in Drosophila models of degeneration.
2026-05-15 | Chromophore-loaded CRALBP mutant proteins restore rod function in chromophore-deficient mice.
Visual function depends critically on the supply of visual chromophore, 11-cis-retinal, to the photoreceptor cells in the retina. Chromophore deficiency due to aging or mutations affecting its delivery and recycling in the eye by the retinal pigment epithelium (RPE) and the Müller cells cause a wide range of visual disorders. The cellular retinaldehyde-binding protein (CRALBP), expressed in both compartments, crucially aids in accelerating the recycling of visual chromophore. Here, we explored the potential of chromophore-loaded CRALBP in restoring vision in chromophore-deficient mice. We tested wild-type human CRALBP and its redox-sensitive A212C:T250C mutant, both pre-loaded with 9-cis-retinal, for their efficacy in delivering chromophore to the retina and restoring rod photoreceptor function in RPE65-deficient mice that cannot produce visual chromophore. We observed robust restoration of rod function both in the isolated retina treated with chromophore-loaded CRALBP and in vivo after a single intravitreal injection of wild-type or mutant CRALBP proteins. Notably, the recovery of rod visual function after exposure to bright light that photoactivated most of the visual pigment was greatly accelerated in CRALBP-treated RPE65-knockout mice compared to wild-type control mice. Together, our results highlight the therapeutic potential of CRALBP complexes in efficiently delivering visual chromophore to retinal rod photoreceptors.
2026-05-11 | CRUMBS-associated mutations in Retinitis Pigmentosa and its impact on molecular scaffolding.
The death of photoreceptors is a primary driver of retinal degenerative diseases, leading to irreversible vision loss. In Retinitis Pigmentosa (RP), a wide spectrum of mutations has been identified. Among these, the Crumbs (CRB) family of proteins, comprising CRB1, CRB2, and CRB3, plays a critical role in maintaining retinal homeostasis. The distribution of CRB mutations indicates population-specific variations, which may be influenced by factors such as founder effects, consanguinity, and geographic isolation. These findings suggest that genetic diagnostics and therapeutic strategies could benefit from considering population diversity. However, genotype-phenotype correlations remain complex, suggesting a modulatory role for genetic modifiers and environmental factors. Dysfunction of the CRB proteins disrupts apicobasal polarity of Retinal Pigment Epithelia (RPE) and photoreceptors, weakening their interaction and impairing phototransduction. This review highlights how mutations in conserved domains, especially the Epidermal Growth Factor (EGF)-like and Laminin G-like regions, compromise structural integrity and trigger degenerative cascades, establishing them as critical biomarkers and promising therapeutic targets for retinal degenerations.
gene therapies
2026-08-11 | Efficacy and safety of AAV RPGR gene therapy in X-linked retinitis pigmentosa: a systematic review and meta-analysis.
X-linked retinitis pigmentosa (XLRP) represents a severe inherited retinal dystrophy associated with pathogenic variants in the retinitis pigmentosa GTPase regulator (RPGR) gene. Adeno-associated virus (AAV)-mediated RPGR gene augmentation is designed to preserve photoreceptor structure and function. The purpose of this study was to critically appraise and quantitatively synthesize the efficacy and safety evidence for AAV-RPGR gene therapy in X-linked retinitis pigmentosa. Scopus, PubMed, the Cochrane Library, ScienceDirect, and Google Scholar were searched from inception through July 11, 2026. Two reviewers independently screened records, two reviewers assessed risk of bias, and extracted data were verified by a second reviewer. Proportions were synthesized using inverse-variance fixed-effect logit models with a 0.5 continuity correction for zero or all-event cells; DerSimonian-Laird random-effects models were used as sensitivity analyses. Cohort linkage, dose-stratified safety, and overlap-adjusted analyses were performed. The search identified 571 records and included 12 clinical reports. Pooled retinal sensitivity improvement was 73.8% (95% confidence interval, 56.0%-86.1%; 25/33 participants), and pooled visual function improvement was 52.3% (95% confidence interval, 38.0%-66.2%; 28/52 participants). The pooled adverse-event proportion was 42.6% (95% confidence interval, 27.2%-59.5%; 42/90 participants), intraocular inflammation was 45.5% (95% confidence interval, 34.6%-56.8%; 36/81 participants), and intraocular-pressure elevation was 34.9% (95% confidence interval, 24.2%-47.4%; 22/63 participants). Product-specific dose analyses showed greater inflammatory or ocular serious adverse-event frequencies at higher vector exposure. AAV-RPGR gene therapy demonstrates clinically relevant functional signals across multiple outcome domains with a structured and monitorable ocular safety profile. Cohort-linked synthesis, dose-specific interpretation, standardized outcome definitions, and long-term multinational follow-up provide a rigorous framework for subsequent clinical development.
2026-08-10 | Defining a Novel RPGR Phenotype of Sector Retinitis Pigmentosa With Cone Dystrophy.
RPGRORF15-associated retinal degeneration is characterized by clinical and genetic heterogeneity: Proximal mutations typically result in rod-cone dystrophy, distal mutations in cone-dominated disease, and mutations within open-reading frame 15 (ORF15) in either phenotype. This study characterizes an intermediate phenotype in which patients exhibit a combination of cone dystrophy and incomplete (sectoral) rod-cone dystrophy associated with mutations in the ORF15 region and explores potential mechanistic explanations. A multinational, multicenter, observational, cross-sectional case series was conducted using databases from RPGR-related retinal dystrophy clinical trial referral centers. Patients with molecularly confirmed RPGR-related cone dystrophy or RPGR-related cone-rod dystrophy were studied. Individuals exhibiting a mixed phenotype of cone dystrophy and sectoral retinitis pigmentosa were identified. In silico analyses assessed the impact of identified mutations on RPGR transcript expression and protein structure. Fourteen patients exhibited a cone dystrophy phenotype with bilateral, symmetrical regions of outer retinal atrophy distributed along the inferior vascular arcades and extending nasally. All harbored ORF15 mutations within a defined transitional zone. All of the mutations were predicted to produce truncated proteins with partial or complete loss of function. Additionally, several were predicted to disrupt splicing regulatory elements. An intermediate phenotype consisting of a cone dystrophy with sectoral retinitis pigmentosa development was characterized. These patients may benefit from full-length RPGR gene therapy. Furthermore, we demonstrate that this rare presentation closely resembles the phenotype observed in some patients with loss-of-function TTLL5-associated cone dystrophy with sectoral involvement.
2026-08-07 | CDHR1-associated retinal degeneration: Clinical phenotypes and therapeutic approaches.
CDHR1 is a recently identified cause of autosomal recessive retinal degeneration manifesting as three distinct clinical phenotypes: macular dystrophy, cone-rod dystrophy or retinitis pigmentosa. In this review, we summarise the discovery and characterisation of CDHR1, clinical phenotypes, natural history and therapeutic approaches including gene supplementation and CRISPR gene editing. CDHR1 is a non-classical cadherin that is highly expressed in cone and rod photoreceptors and is essential for the higher-order organisation of the functionally critical outer segments. Promising pre-clinical data show that AAV gene supplementation therapy delivered by subretinal injection can lead to long-term morphological, structural, functional and behavioural improvements in the Cdhr1 knockout mouse model. Notably, CDHR1 supplementation restored full-length photoreceptor outer segments that are usually shortened and disorganised in disease models and prolonged photoreceptor survival - key mechanisms for the functional and behavioural rescue effects that were observed. The disease is likely to be underdiagnosed because CDHR1-associated macular dystrophy - likely to be the most common disease phenotype - is most often caused by a 'silent' nucleotide substitution that has previously been overlooked by genetic testing. Since the macular dystrophy phenotype has phenotypic similarities to advanced dry age-related macular degeneration (AMD), misdiagnoses are common. CDHR1-associated macular dystrophy also shares phenotypic features with a variety of monogenic masquerades such as ABCA4, PRPH2 and GUCY2D-associated macular dystrophies; we present a flowchart to guide the clinical distinction of these disorders which is now critical for patients as their treatments diverge. AAV gene therapy may be beneficial across the CDHR1 disease spectrum - including those with hypomorphic variants associated with macular dystrophy or retinitis pigmentosa. The coding sequence fits into AAV and with the macular dystrophy phenotype, there is a large time window for potential intervention and a large treatable population. Hence clinical trials are anticipated. It is therefore important that patients with CDHR1-associated retinal degeneration are accurately phenotyped and genetically confirmed to support the application of CDHR1 gene therapy.
2026-08-03 | Identification of a Duplication in the RP17 Locus in an Individual With Pathogenic CEP290 Variants: Implications for RP17 Variant Classification.
To assess the pathogenicity of a novel duplication in the RP17 locus identified in a cone dystrophy proband with biallelic CEP290 variants. Structural variants (SVs) in this locus have previously been associated with dominant retinitis pigmentosa. Inheritance of the duplication was assessed by breakpoint polymerase chain reaction (PCR). Ophthalmic evaluation included fundus examination, multimodal retinal imaging, and full-field electroretinogram (ERG). A proband-derived pluripotent stem cell line was differentiated into photoreceptor precursor cells (PPCs) and retinal organoids (ROs). Variant-induced mis-splicing of CEP290 was assessed by reverse-transcription PCR (RT-PCR) and long-read cDNA sequencing, and immunohistochemistry was used to assess photoreceptor morphology. Expression of GDPD1 was quantified by quantitative RT-PCR. The proband and father carried the 324-kb duplication in the RP17 locus. The father was clinically unaffected, but the proband showed features of cone dystrophy, including reduced visual acuity, foveal abnormalities, diminished cone density, and preserved dark-adapted but absent light-adapted ERG responses. The compound heterozygous variants in CEP290 resulted in pseudoexon inclusion and exon 36 skipping in patient-derived retinal cells. Immunohistochemistry revealed altered ciliation and reduced trafficking of L/M opsin and rhodopsin in ROs. In silico modeling predicted that the novel RP17 duplication does not disrupt chromatin looping, and GDPD1 expression was not upregulated in patient ROs, in contrast to pathogenic RP17-SVs. The cone dystrophy phenotype of the proband can be attributed to the CEP290 variants, whereas the novel RP17 duplication can be classified as likely benign based on the integrated evidence. These findings emphasize the importance of modeling and functional studies for accurately classifying RP17-SVs and preventing misinterpretation in clinical diagnostics.
2026-07-15 | Cone-Rod Dystrophy PCARE-Associated Retinopathy.
Background and Clinical Significance: Biallelic pathogenic variants in the PCARE gene (photoreceptor cilium actin regulator), also known as C2orf71 (chromosome 2 open reading frame 71), are typically associated with retinitis pigmentosa type 54 (RP54) and, less frequently, with cone-rod dystrophy (CORD23). Case Presentation: A 52-year-old man presented with an eight-year history of progressive visual loss, without photophobia or nyctalopia. He underwent a comprehensive ophthalmological evaluation, including multimodal retinal imaging, automated perimetry, and full electrophysiological testing, in accordance with International Society for Clinical Electrophysiology of Vision (ISCEV)'s standards. Genetic testing was performed using next-generation sequencing (NGS) with an inherited retinal dystrophy gene panel, and findings were confirmed by Sanger sequencing. Clinical examination revealed bilateral macular atrophy with minimal foveal sparing and a central scotoma. Optical coherence tomography (OCT) showed disruption of the outer retinal layers and retinal pigment epithelium (RPE) abnormalities. Fundus autofluorescence (FAF) demonstrated central hypoautofluorescence surrounded by a hyperautofluorescent ring. Electrophysiological testing revealed severely reduced rod- and cone- mediated responses on full-field electroretinography (ERG), absent pattern ERG responses, and markedly reduced multifocal ERG responses, indicating widespread retinal dysfunction with significant macular involvement. Genetic analysis identified a homozygous pathogenic nonsense variant in PCARE [c.3289C>T; p.(Gln1097*)], confirming the diagnosis of an autosomal recessive inherited retinal dystrophy. Conclusions: Biallelic PCARE variants can cause late-onset severe retinal dystrophy, with predominant macular involvement and cone-rod dysfunction. Given its phenotypic overlap with other inherited retinal diseases, accurate diagnosis requires the integration of multimodal retinal imaging, electrophysiological testing, and comprehensive genetic analysis.
cell therapies
2026-07-09 | Photoreceptor-targeted engineered exosomes encapsulating black phosphorus quantum dots for alleviating photoreceptor degeneration.
Photoreceptor degeneration is a major cause of irreversible visual impairment worldwide, most notably in retinitis pigmentosa (RP). Here, we developed a dual-targeted therapeutic nanoplatform by loading black phosphorus quantum dots (BPQDs) into human dental pulp mesenchymal stem cell-derived exosomes (hDPSC-Exos) and surface-modifying with cell-penetrating peptide transactivated transcription (TAT) and photoreceptor-specific peptide MH42, namely TAT/MH42-engineered black phosphorus quantum dot-loaded exosomes (M/T-BPQD@Exos). M/T-BPQD@Exos showed typical exosomal morphology and good uniformity. In vitro, M/T-BPQD@Exos effectively protected 661 W photoreceptor cells against N-methyl-N-nitrosourea (MNU) injury. In vivo, M/T-BPQD@Exos specifically accumulated in the outer nuclear layer (ONL) and significantly preserved retinal structure and visual function in MNU-induced photoreceptor degeneration rats. Biosafety assessment confirmed no obvious systemic toxicity and inflammation. Mechanistically, M/T-BPQD@Exos alleviated calcium overload, maintained mitochondrial integrity, and suppressed mitochondrial apoptosis by regulating Bcl-2, Bax, and cleaved caspase-3. This study provides a safe and precise strategy for photoreceptor protection in retinal degenerative diseases.
2026-05-31 | Stem cell therapy in retinal disease.
Stem cell therapy presents a new solution to cure degenerative diseases of the retina, which normally have limited ability to regenerate after injury. Stem cells are cells capable of self-renewal and differentiation into more specialized cells, and can be derived from both embryonic and adult sources. This definition encompasses a heterogeneous group of cells possessing varied potency and characteristics. Current attempts in applying stem cell technology to the retina have primarily focused on regenerating the retinal pigment epithelium (RPE) and light-sensing photoreceptor cells. They have not only shown the ability to prevent the death of host photoreceptors, but they can also differentiate into all major retinal cell types to replace lost cells. In vivo experiments, primarily performed in mice, have found that stem cell-derived RPE cells, photoreceptors, and their precursors can survive long-term in animal models without tumorigenicity or immune rejection. Following transplantation, these cells were able to integrate and mature in vivo, forming synapse-like structures with host retinal cells. Furthermore, transplants in mice were able to rescue visual function at a cellular and behavioral level. These promising preclinical results have led to clinical trials testing cell therapy in numerous diseases, including Stargardt macular dystrophy, age-related macular degeneration, retinitis pigmentosa, and central retinal vein occlusion. These trials have demonstrated the safety of cell therapy and have improved visual function in some patients. Scientific advances in the culturing of retinal organoids and the understanding of cell redifferentiation are informing the development of better stem cell therapies, which hold great potential for restoring vision to patients with retinal dystrophies.
2026-05-27 | Subtenon Autologous Platelet-Rich Plasma in Degenerative Retinal Diseases: A Prospective Pilot Study of Safety and Exploratory Functional Signals in Retinitis Pigmentosa and EMAP.
Purpose: To evaluate the safety and feasibility of repeated subtenon administration of autologous platelet-rich plasma (PRP) in patients with degenerative retinal diseases and to explore preliminary, hypothesis-generating functional observations in retinitis pigmentosa (RP) and extensive macular atrophy with pseudodrusen-like appearance (EMAP). Methods: This prospective, open-label, uncontrolled pilot study included 13 patients (6 RP, 7 EMAP) who received three subtenon PRP injections (1.5 mL each) at baseline, Month 2, and Month 4, with follow-up through Month 6. The study was designed primarily to assess safety and feasibility and was not powered or intended to evaluate efficacy. The primary outcome was safety, including adverse events and intraocular pressure changes. Exploratory secondary outcomes included best-corrected visual acuity (BCVA, logMAR), visual field mean deviation (MD), and structural optical coherence tomography (OCT) parameters. Electrophysiological outcomes were analyzed descriptively due to incomplete paired data. Analyses were conducted within diagnostic groups, and no between-group comparisons were performed. Results: All 13 patients completed the study. No serious adverse events or permanent ocular morbidity were observed. Two transient and self-limited adverse events occurred (anterior uveitis and intraocular pressure elevation), both resolving without sequelae. In the overall cohort, BCVA remained stable without statistically significant change. In the RP subgroup, a small exploratory change in BCVA was observed (mean ΔlogMAR -0.09; nominal p = 0.048), corresponding to approximately 4-5 ETDRS letters; however, this finding was associated with wide confidence intervals and limited statistical power and should be interpreted cautiously. In the EMAP subgroup, functional stability was observed without evidence of consistent improvement. Visual field mean deviation and OCT findings were consistent with absence of short-term deterioration across available paired data. Electrophysiological outcomes showed no consistent directional change. Conclusions: Repeated subtenon PRP administration appeared feasible and well tolerated in this small, uncontrolled pilot cohort. Any observed functional changes are preliminary and hypothesis-generating only and do not establish efficacy. Larger, adequately powered controlled studies with standardized endpoints are required to determine the potential role of PRP in degenerative retinal diseases.
2026-05-15 | Inhibitory Circuits Can Restore OFF Pathway Responses in Retinal Prostheses.
One of the first steps in processing visual information is to split the light signal captured by photoreceptors into complementary ON and OFF pathways, which separately encode increases and decreases in luminance. In blind patients with retinal degeneration, optoelectronic prostheses can successfully activate the ON pathway and evoke bright percepts; however, patients do not perceive dark features. This indicates that the OFF pathway is not being activated by existing prosthetics. To quantify OFF pathway deficits, we stimulated retinal ganglion cells (RGCs) in a mouse model of retinitis pigmentosa of either sex with electrical stimulation mimicking retinal prosthetic activation and recorded their voltage responses using whole-cell recording. We found that most OFF RGCs respond with incorrect ON responses, except for one specific subtype of RGC, the OFFα, which retained correct OFF-type responses following the termination of stimulation. We found that these preserved OFF responses were driven by postinhibitory rebound excitation, mediated by hyperpolarization-activated cyclic nucleotide-gated channels. Using a combinatorial genetic approach to achieve chemogenetic control, we identified AII amacrine cells as the presynaptic source driving these electrically evoked OFF responses. These insights into how the OFF pathway responds to artificial stimulation suggest new opportunities to improve prosthetic vision restoration through tuning of stimulation parameters.
2026-05-03 | Retinal organoids: current status of development and new avenues for application in disease modeling, drug discovery and therapeutics.
Visual impairment affects over 2.2 billion people worldwide and the major causes include age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. For research in these areas, although animal models offer a more physiologically complex system than in vitro approaches, their use raises ethical considerations, and species-specific differences such as variations in protein sequences and signaling pathways. This can limit the direct translatability of the outcomes. Traditional 2-D cell cultures, in contrast, lack the multicellular organization and dynamic microenvironment necessary to replicate human retinal complexity. Retinal organoids (ROs), three-dimensional tissue constructs derived from pluripotent stem cells, have emerged as a promising model due to their human origin and complex cellular interactions that cannot be achieved in conventional 2-D/3-D co-culture models. In this review, we provide a brief overview of the evolution from 2-D to 3-D retinal models, highlight the structural and functional features of ROs including the presence of layered retinal architecture, photoreceptor outer segment formation, and light-responsive electrophysiological activity and summarize their applications in disease modeling, drug discovery, and gene and cell therapy. ROs represent a significant advancement over traditional models by enabling the recapitulation of human-specific retinal development, facilitating the study of patient-derived disease phenotypes, and providing a platform for personalized therapeutic screening. Their development has deepened understanding of pathological mechanisms in conditions such as retinitis pigmentosa and AMD, while enabling preclinical testing of targeted interventions like CRISPR-based gene editing and photoreceptor cell replacement. Nonetheless, challenges remain in fully replicating retinal vascularization, long-term functional maturation, and synaptic connectivity, underscoring the need for continued refinement and integration with complementary model systems.
other
2026-07-24 | DNAJC17 deficiency: A novel inborn error of immunity with TNF-driven autoinflammation.
Inborn Errors of Immunity (IEI) encompass a broad spectrum of monogenic disorders with variable clinical presentations, including recurrent infections, autoimmunity, and systemic inflammation. Loss-of-function mutations in DNAJC17 have been previously linked to retinal dystrophy and hypogammaglobulinemia; however, the complete immunological phenotype and underlying autoinflammatory mechanisms remain poorly characterized. We conducted a comprehensive clinical, molecular, and immunological investigation of three affected individuals from two unrelated consanguineous families. Our evaluation included whole genome sequencing with systematic exclusion of alternative genetic etiologies, quantitative analysis of DNAJC17 mRNA expression, and assessment of intracellular DNAJC17 protein levels. In addition, we performed in-depth immunophenotyping of adaptive and innate immune cell subsets, cytokine profiling, and interferon-stimulated gene expression analysis, alongside longitudinal evaluation of responses to therapeutic interventions. All three patients presented with early-onset retinitis pigmentosa, recurrent fever, lymphadenitis, and hypogammaglobulinemia. Sanger sequencing confirmed a homozygous variant (c.681G>A; p.Ala227=) in DNAJC17 resulting in exon 9 skipping. Comprehensive whole genome analysis excluded pathogenic variants in other immune-related genes. Quantitative RT-PCR demonstrated reduced DNAJC17 mRNA levels and flow cytometry showed decreased intracellular protein levels, consistent with a hypomorphic loss-of-function effect. Immunological evaluation revealed distinct abnormalities in T, B, and NK-cell subsets, with altered monocyte and dendritic cell populations indicating innate and adaptive immune dysregulation. Inflammatory profiling identified increased cytokine activity, including TNF-α and IL-6, alongside mild induction of interferon-stimulated genes. Conventional immunomodulatory therapies failed to achieve sustained remission. In contrast, TNF inhibitor therapy resulted in dramatic clinical improvement with normalization of inflammatory markers, sustained for over three years without significant adverse events. Our findings establish DNAJC17 deficiency as a novel monogenic inborn error of immunity characterized by retinopathy, combined immunodeficiency, and TNF-driven autoinflammation responsive to targeted TNF blockade. The underlying immune abnormalities underscore the essential role of DNAJC17 in maintaining immune homeostasis and mitochondrial function. This work provides mechanistic insights into disease pathogenesis and establishes a rational, precision medicine therapeutic approach for this newly defined syndrome.
2026-06-11 | Multimodal imaging and intravitreal faricimab for polypoidal choroidal vasculopathy associated with a choroidal nevus in genetically confirmed Usher syndrome type 2: a case report.
Usher syndrome is an autosomal recessive disorder characterized by retinitis pigmentosa (RP), sensorineural hearing loss, and vestibular dysfunction. Polypoidal choroidal vasculopathy (PCV) is characterized by branching neovascular networks and polypoidal lesions. While typically classified within the pachychoroid spectrum, PCV can also manifest in eyes without choroidal thickening. Conversely, RP is usually associated with choroidal thinning, which may lead to underdiagnosis of PCV. To the best of our knowledge, PCV has not previously been reported in patients with Usher syndrome. Here, we present the first genetically confirmed case of Usher syndrome type 2 complicated by PCV that was successfully managed with intravitreal faricimab. A 63-year-old man presented with night blindness. The diagnosis of Usher syndrome type 2 was confirmed based on bilateral RP features, moderate sensorineural hearing loss, and two pathogenic USH2A variants. Six years after the initial diagnosis, the patient developed visual disturbance in the left eye, with the best-corrected visual acuity (BCVA) declining to 20/80. Multimodal imaging, including spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography angiography, confirmed the diagnosis of PCV. An amelanotic choroidal nevus was also identified on SD-OCT. After five intravitreal faricimab injections, the BCVA improved to 20/30, with a 75% reduction in pigment epithelial detachment height and complete subretinal fluid resolution without adverse effects. To our knowledge, this is the first reported case of PCV associated with a choroidal nevus in a patient with genetically confirmed Usher syndrome type 2. PCV should not be excluded in patients with RP despite characteristic choroidal thinning. Intravitreal faricimab was effective and well-tolerated, suggesting its therapeutic potential in such cases.
2026-06-04 | Targeted antisense oligonucleotide therapy rescues PRPF31 expression in retinitis pigmentosa caused by a splicing mutation.
Pathogenic variants in splicing factors are the second most common cause of autosomal dominant retinitis pigmentosa, with mutations in PRPF31 being the most prevalent. Here, we characterize a novel intronic variant in PRPF31 (c.1074-11C>G) that creates a cryptic 3' splice site, resulting in an aberrantly spliced transcript predicted to encode a protein with an altered C terminus. However, the pathogenic protein is unstable and undetectable in patient-derived induced pluripotent stem cells (iPSCs). In addition, expression of the full-length PRPF31 protein was reduced in patient-derived retinal pigment epithelium (RPE). To correct the splicing defect, we designed a panel of antisense oligonucleotides (ASOs) targeting putative RNA-binding sites in exon 10 and intron 10 and identified a candidate that corrects PRPF31 splicing in a minigene reporter system as well as in patient-derived iPSCs and RPE. We further showed that ASO treatment enhances PRPF31 protein expression in patient-derived iPSC and RPE carrying the intronic mutation, supporting the potential of the ASO-based approach to restore PRPF31 expression in patients with the same or similar splicing defects.
2026-05-27 | TPM1 drives cytoskeleton-immunometabolism coupling and LGALS9/CD45-mediated neuroinflammatory propagation in retinitis pigmentosa.
Retinitis pigmentosa (RP), the most prevalent inherited retinal degeneration, features progressive photoreceptor loss with no approved disease-modifying therapies. While microglia-driven neuroinflammation accelerates RP progression, its sustaining mechanisms remain elusive. Through integrated multiomics profiling of retinal degeneration 10 (rd10) mice, we identify tropomyosin 1 (TPM1) as a previously unrecognized cytoskeletal-immune regulator orchestrating spatial neuroinflammation in RP. Genetic ablation of Tpm1 attenuated microglial reactivity and preserved vision, whereas overexpression triggered self-reinforcing inflammation via four interlocked axes: (i) TPM1-mediated activator protein-1 (AP-1) hyperactivation initiates senescence-associated secretory phenotype (SASP) through mitogen-activated protein kinase (MAPK) kinase/extracellular signal-regulated kinase 3-dependent MAPK signaling; (ii) SASP subsequently mediates reduced phagocytosis; (iii) Tpm1-Apoe/Fabp5 axis disruption precipitates lipid droplet accumulation with cholesterol crystallization; (iv) galectin-9 (LGALS9)/CD45-mediated intermicroglial signaling propagates inflammatory signals across the retina. Our work redefines TPM1 as a linchpin in self-sustaining neurodegeneration cycles, where cytoskeletal dysfunction fuels immunometabolic collapse. These findings unveil precision therapeutic strategies targeting TPM1 hubs-notably the LGALS9/CD45 axis-to disrupt inflammatory cycles while preserving retinal homeostasis.
2026-05-20 | Intravitreal Adalimumab in Retinitis Pigmentosa: A Prospective Pilot Study Assessing Ocular Safety and Feasibility.
Objective The objective of this study was to evaluate the short-term ocular safety, feasibility, and exploratory functional signals associated with intravitreal adalimumab (ADA) in patients with retinitis pigmentosa (RP). Methods This prospective, single-arm pilot study included 21 patients with RP who received intravitreal adalimumab (2 mg/0.05 mL) at baseline, month 2, and month 4, with follow-up to month 6. The primary objective was to assess ocular safety and treatment feasibility. Exploratory functional outcomes included best-corrected visual acuity (BCVA, logarithm of the minimum angle of resolution (LogMAR)) and automated perimetry parameters (mean deviation (MD), pattern standard deviation (PSD), and Field Preservation Deviation Index (FPDI)). Structural assessment was performed using optical coherence tomography (OCT). Analyses compared baseline and month 6 outcomes using paired statistical methods. BCVA values were analyzed at the patient level as the mean of both eyes. Results All scheduled intravitreal injections were successfully completed, and no serious ocular adverse events were observed during follow-up. Mean BCVA showed no statistically significant change from baseline to month 6 (0.76 to 0.70 LogMAR; p = 0.115). Visual field parameters (MD, PSD, and FPDI) remained stable, with no statistically significant differences over time. OCT findings demonstrated advanced baseline structural alterations consistent with RP, without evidence of treatment-related anatomical deterioration or cystoid macular edema during follow-up. Flicker electroretinography (ERG) responses were measurable in a limited subset of patients and were analyzed descriptively, showing no consistent evidence of decline. Conclusions In this prospective pilot study, intravitreal adalimumab demonstrated a favorable short-term ocular safety profile and was feasible to administer in patients with retinitis pigmentosa. No significant functional or structural changes were observed over six months. These findings are hypothesis-generating and support the need for controlled studies to further evaluate the safety and potential role of tumor necrosis factor alpha (TNF-α) inhibition in inherited retinal degeneration.
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Drug Discovery Landscape
97 orphan drug designations for Retinitis pigmentosa, including 1 approved therapy.
97 orphan drug designations for Retinitis pigmentosa, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
retinal cells derived from allogeneic human induced pluripotent stem cell line | cell therapies | FDA | 2026-03-26 | — | Agnos Therapeutics, Inc. |
tripentadecanoin | small molecules | FDA | 2026-03-23 | — | SunRegen Healthcare AG |
allogeneic self-organized three-dimensional retinal tissue-sheet derived from human induced pluripotent stem cells (iPSCs) that include photoreceptor precursors | cell therapies | FDA | 2026-03-12 | — | Sumitomo Pharma America Inc |
a cell-based therapeutic composed of purified human rod precursor cells (hRPCs) | cell therapies | FDA | 2026-02-14 | — | InGel Therapeutics Inc. |
allogeneic human induced pluripotent stem cell-derived photoreceptor precursor cells | cell therapies | FDA | 2025-12-10 | — | BlueRock Therapeutics LP |
recombinant adeno-associated virus vector expressing ChronosFP | gene therapies | FDA | 2025-05-01 | — | Bionic Sight, Inc. |
N6-(3-aminopropyl)-L-lysine trihydrochloride | small molecules | FDA | 2025-04-16 | — | Ren Bioscience LLC |
adeno-associated virus vector with a codon-optimized chicken Opsin 5 gene | gene therapies | FDA | 2025-03-03 | — | GenAns Biotechnology Co., Ltd |
4-[[(4-Methoxyphenyl)thio]methyl]-N,N-dimethyl-1H-1,2,3-triazole-1-ethanamine | small molecules | EMA | 2024-11-11 | — | Miramoon Pharma S.L. |
recombinant human adeno-associated virus serotype 2 containing PsCatCh2.0 gene | gene therapies | FDA | 2024-10-28 | — | Zhongmou Therapeutics, Inc. |
adeno associated virus carrying opn3 | gene therapies | FDA | 2024-09-25 | — | NeoVec Biotherapeutics Inc. |
recombinant adeno-associated virus 5 vector expressing a functional human cyclic nucleotide gated channel subunit beta 1 (CNGB1) gene | gene therapies | FDA | 2024-09-23 | — | National Institutes of Health National Institutes of Health (NIH), National Center for Advancing Translational Sciences (NCATS) |
adeno-associated virus (AAV) gene therapy product that comprised a modified AAV2 capsid and a light sensitive transgene | gene therapies | FDA | 2024-08-20 | — | Skyline Therapeutics (US) Inc. |
(E)-2-((4-((4-Benzyl(ethyl)amino)phenyl)diazinyl)phenyl)amino-N,N,N-triethyl-2-oxoethan-1-aminium chloride | small molecules | EMA | 2024-07-25 | — | Kiora Pharmaceuticals GmbH |
Human induced pluripotent stem cells (iPSC)-derived Photoreceptor Progenitor Cells | cell therapies | FDA | 2024-03-20 | — | iRegene Therapeutics Co., Ltd |
2-(4-(((4-methoxyphenyl)thio)methyl)-1H-1,2,3-triazol-1-yl)-N,N-dimethylethan-1-aminium hydrochloride | small molecules | FDA | 2024-01-22 | — | Miramoon Pharma SL |
Recombinant adeno-associated virus type 5 vector containing codon optimized human RPGR^ORF15 protein coding gene (rAAV5-hRPGR^ORF15) | gene therapies | FDA | 2024-01-22 | — | FTGEN Corp. |
Human Retinal Pigment Epithelial Cell Injection | cell therapies | FDA | 2023-09-19 | — | Eyecure Therapeutics Inc. |
Adeno-associated viral vector serotype 2.NN encoding the human cyclic nucleotide-gated channel subunit A1 gene | gene therapies | FDA | 2023-08-17 | — | ViGeneron GmbH |
Human Nuclear Hormone Receptor Subfamily 2 Group E Member 3 (hNR2E3) | gene therapies | FDA | 2022-12-15 | — | Ocugen, Inc. |
adeno-associated virus serotype 8 expressing Cas9 gene and single guide RNA targeting R135W mutation in Rhodopsin gene | gene therapies | FDA | 2022-07-14 | — | Chigenovo Co., Ltd. |
AAV2/8-SaCas9-sgRNA RHO-T17M | gene therapies | FDA | 2022-06-07 | — | Chigenovo Co., Ltd. |
Adeno-associated virus serotype R100 containing the human RPGRorf15 gene isoform | gene therapies | EMA | 2022-05-16 | — | Pharma Gateway AB |
Benzyl ethyl aminoazobenzene quaternary ammonium | small molecules | FDA | 2022-03-17 | — | Kiora Pharmaceuticals, Inc. |
Methotrexate | small molecules | FDA | 2021-07-21 | — | Aldeyra Therapeutics, Inc. |
Melatonin | small molecules | EMA | 2021-05-20 | — | Worphmed S.r.l. |
Melatonin | small molecules | FDA | 2021-05-10 | — | WORPHMED Srl |
Small molecule inhibitor of kinase mediators of the Wnt pathway | small molecules | FDA | 2021-04-16 | — | Endogena Therapeutics, Inc, |
(+)-5-chloro-1-ethyl-3-(2-hydroxy-3-methoxybenzyl)-2-oxoindolin-3-yl dimethylcarbamate | small molecules | FDA | 2021-03-16 | — | MitoChem Therapeutics, Inc. |
Adeno-associated virus serotype 5 containing the human NR2E3 gene | gene therapies | EMA | 2021-02-19 | — | Ocugen Limited |
Chemically induced photoreceptor-like cells | proteins | FDA | 2021-02-18 | — | CiRC Biosciences, Inc. |
DNA plasmid encoding human transferrin gene | oligonucleotides | EMA | 2020-11-13 | — | PulseSight Therapeutics |
DNA plasmid encoding the human transferrin gene | gene therapies | FDA | 2020-09-25 | — | PulseSight Therapeutics |
Adeno-associated virus serotype 2/8 vector containing the human PDE6A gene | gene therapies | EMA | 2020-08-21 | — | Institute For Ophthalmic Research |
Adeno-Associated Virus containing the gene for human Nuclear Hormone Receptor NR2E3 (AAV-hNR2E3) | gene therapies | FDA | 2020-08-07 | — | Ocugen Inc. |
sulindac | small molecules | FDA | 2020-08-04 | — | Prolindox, Inc. |
Adeno-associated viral vector serotype 8 containing cDNA of the human PDE6A protein | gene therapies | FDA | 2020-03-09 | — | Universitätsklinikum Tübingen (UKT) |
antisense oligonucleotide targeting the P23H mutation of the RHO gene | oligonucleotides | FDA | 2019-11-18 | — | ProQR Therapeutics IV B.V. |
2'-O-(2-methoxyethyl)-modified antisense oligonucleotide targeting exon 13 in the USH2A gene | oligonucleotides | EMA | 2018-02-22 | — | Laboratoires Thea |
Adenovirus-associated viral vector serotype 8 containing the human RPGR gene | gene therapies | EMA | 2018-02-22 | — | Biogen Netherlands B.V. |
2¿-O-(2-methoxyethyl) modified antisense oligonucleotide targeting exon 13 in the USH2A gene | oligonucleotides | FDA | 2017-11-20 | — | Laboratoires Théa |
Adeno Associated Virus carried Multi Characteristic Opsin | gene therapies | FDA | 2017-10-03 | — | Nanoscope Therapeutics Inc. |
Antisense oligonucleotide targeting exon 13 in the USH2A gene | oligonucleotides | EMA | 2017-08-23 | — | ProQR Therapeutics IV BV |
Lens epithelial derived growth factor (1-326) | proteins | EMA | 2017-08-23 | — | Dorian Regulatory Affairs B.V. |
recombinant adeno-associated virus vector expressing the retinitis pigmentosa GTPase regulator | gene therapies | FDA | 2017-07-31 | — | Beacon Therapeutics |
antisense oligonucleotide targeting exon 13 of the USH2A gene | oligonucleotides | FDA | 2017-07-27 | — | ProQR Therapeutics IV B.V. |
antisense oligonucleotide targeting the c.7595-2144A>G mutation in intron 40 of the USH2A gene | oligonucleotides | FDA | 2017-06-28 | — | ProQR Therapeutics IV B.V. |
Antisense oligonucleotide targeting the USH2A gene | oligonucleotides | EMA | 2017-03-20 | — | ProQR Therapeutics IV BV |
adeno-associated viral vector serotype 2.7m8 containing the chrimsonR-tdTomato gene | gene therapies | FDA | 2017-01-25 | — | GenSight Biologics |
Adeno-associated viral vector serotype 8 encoding engineered rhodopsin DNA-binding repressor and human rhodopsin expression cassettes | gene therapies | EMA | 2016-12-12 | — | Fondazione Telethon Ets |
adenovirus associated viral vector serotype 5 containing the RPGR gene | gene therapies | FDA | 2016-11-29 | — | Janssen Research & Development, LLC |
Adeno-associated viral vector serotype 5 containing the human RLBP1 gene | gene therapies | EMA | 2016-10-14 | — | Coave Therapeutics |
Adeno-associated viral vector serotype 2/2 containing a gene encoding the channelrhodopsin-2 protein [RST-001] | gene therapies | EMA | 2016-10-14 | — | Allergan Pharmaceuticals International Limited |
Adenovirus associated viral vector serotype 5 containing the human RPGR gene | gene therapies | EMA | 2016-08-29 | — | Janssen-Cilag International N.V. |
Adeno-associated viral vector serotype 2.7m8 containing the ChrimsonR-tdTomato gene | gene therapies | EMA | 2016-07-14 | — | GenSight- Biologics |
adenovirus-associated viral vector serotype 5 containing the human pde6B gene | gene therapies | FDA | 2016-07-05 | — | eyeDNA Therapeutics |
4-((2E)-1-oxo-3-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-propen-1-yl)-1-piperazinecarboxamide | small molecules | EMA | 2016-05-30 | — | Shire Pharmaceuticals Ireland Limited |
Recombinant adeno-associated viral vector containing the human RPGR gene | gene therapies | EMA | 2016-05-30 | — | FGK Representative Service GmbH |
Allogeneic fetal human retinal progenitor cells expanded ex vivo | cell therapies | EMA | 2016-02-17 | — | Voisin Consulting Life Sciences |
4-[(2E)-1-Oxo-3-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-propen-1-yl]-1-piperazinecarboxamide | small molecules | FDA | 2016-02-08 | — | Shire HGT, Inc. |
Adenovirus-associated viral vector serotype 2 containing the human RPE65 gene [Luxturna] | gene therapies | EMA | 2015-07-28 | 2018-12-05 | Novartis Europharm Limited |
Recombinant human mesencephalic astrocyte-derived neurotrophic factor | proteins | EMA | 2015-04-24 | — | Regintel Limited |
Sodium 3-[(4aR,6R,7R,7aS)-7-hydroxy-2-oxido-2-sulfanylidene-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-2-bromo-6-phenyl-5H-imidazo[1,2-a]purin-9-one | gene editing enzymes | EMA | 2015-03-19 | — | Universitätsklinikum Tübingen (UKT) |
Myriocin | small molecules | EMA | 2015-02-12 | — | Nanovector s.r.l. |
human recombinant mesencephalic, astrocyte derived neurotrophic factor | proteins | FDA | 2014-12-22 | — | Amarantus BioScience Holdings, Inc. |
non-replicating recombinant adeno-associated virus vector containing a fragment of the gene encoding channelrhodopsin-2 protein | gene therapies | FDA | 2014-10-20 | — | Allergan, Inc. |
all-cis-docosa-4,7,10,13,16,19-hexaenoic acid | small molecules | FDA | 2014-05-21 | — | Celavista Mitobiogenesis, S.L. |
recombinant lens epithelium derived growth factor 1-326 | proteins | FDA | 2014-05-19 | — | Ocugen, Inc. |
N-acetyl cysteine amide | small molecules | FDA | 2013-12-31 | — | Nacuity Pharmaceuticals, Inc. |
expanded human allogeneic neural retinal progenitor cells extracted from neural retina | cell therapies | FDA | 2013-08-22 | — | ReNeuron Ltd |
recombinant human nerve growth factor | proteins | FDA | 2013-08-08 | — | Dompe S.p.A. |
Adenovirus associated viral vector serotype 5 containing the human pde6ß gene | gene therapies | EMA | 2013-06-19 | — | eyeDNA Therapeutics |
Expanded human allogeneic neural retinal progenitor cells extracted from neural retina | cell therapies | EMA | 2013-06-19 | — | Reneuron Ireland Limited |
Unoprostone isopropyl | small molecules | EMA | 2013-06-19 | — | [INACTIVE] Pharmalex UK Services Limited |
Recombinant human nerve growth factor | proteins | EMA | 2013-06-07 | — | Dompé farmaceutici S.p.A. |
Encapsulated human retinal pigment epithelial cell line transfected with plasmid vector expressing human ciliary neurotrophic factor | cell therapies | EMA | 2013-01-24 | — | Le4d Global Regulatory Science Limited |
adeno-associated viral vector containing DNA encoding an RNAi targeting rhodopsin in combination with an adeno-associated viral vector containing DNA encoding a rhodopsin gene | gene therapies | FDA | 2012-12-13 | — | Spark Therapeutics Ireland Ltd. |
Adeno-associated viral vector serotype 8 encoding an inducible short hairpin RNA targeting claudin-5, Alvespimycin [AT-0002] | gene therapies | EMA | 2012-11-28 | — | [INACTIVE] Alimentary Health Limited |
Adeno-associated viral vector serotype 8 encoding an inducible short hairpin RNA targeting claudin-5, Alvespimycin | small molecules | EMA | 2012-11-08 | — | [INACTIVE] Alimentary Health Limited |
human retinal progenitor cells | cell therapies | FDA | 2012-07-23 | — | jCyte, Inc. |
Recombinant human methionine proinsulin | proteins | EMA | 2012-04-26 | — | ProRetina Therapeutics S.L. |
9-cis-Retinyl acetate | small molecules | EMA | 2011-05-13 | — | Granzer Regulatory Consulting & Services GmbH |
Adeno-associated viral vector serotype 5 containing a rhodopsin gene [GT038] | gene therapies | EMA | 2010-12-17 | — | [INACTIVE] Spark Therapeutics Ireland Limited |
zuretinol acetate | small molecules | FDA | 2010-12-02 | — | Retinagenix LLC |
unoprostone isopropyl | small molecules | FDA | 2010-09-16 | — | R-Tech Ueno, Ltd. |
Epitalon | peptides | FDA | 2010-09-02 | — | BioDiem Ltd |
Recombinant human proinsulin | proteins | EMA | 2009-02-11 | — | ProRetina Therapeutics S.L. |
recombinant human proinsulin (Including rhPI-Methionine) | proteins | FDA | 2008-12-10 | — | ProRetina Therapeutics, S.L. |
Palucorcel [CNTO2476] | cell therapies | EMA | 2008-04-01 | — | Janssen Biologics B.V. |
recombinant human rod-derived cone viability factor | proteins | FDA | 2008-01-07 | — | Fovea Pharmaceuticals |
Rod-derived cone viability factor, recombinant | proteins | EMA | 2007-11-29 | — | [INACTIVE] Fovea Pharmaceuticals |
Adenovirus associated viral vector serotype 4 containing the human RPE65 gene | gene therapies | EMA | 2007-11-14 | — | Coave Therapeutics |
4,7,10,13,16,19-docosahexaenoic acid | small molecules | EMA | 2006-11-03 | — | Celavista Mito-Biogenesis S.L. |
Human umbilical tissue-derived cells | cell therapies | FDA | 2006-03-13 | — | Janssen Research & Development, LLC |
Urea for intravitreal injection | gene therapies | FDA | 2005-12-14 | — | Vitreo Retinal Techologies, Inc |
revakinagene taroretcel | cell therapies | FDA | 2004-09-01 | — | Neurotech USA, Inc. |
Gangliosides as sodium salts | small molecules | FDA | 1988-11-17 | — | Fidia Pharmaceutical Corp. |
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