RARE DISEASE
X-linked retinoschisis
X-linked retinoschisis
X-linked retinoschisis
Synonyms: X-linked juvenile retinoschisis, XLRS
Synonyms: X-linked juvenile retinoschisis, XLRS
Synonyms: X-linked juvenile retinoschisis, XLRS
Drug discovery
8
drugs
With orphan designations
Overview
X-linked retinoschisis (XLRS) is an inherited retinal disorder affecting males, caused by mutations in the RS1 gene (Xp22.1) leading to impaired retinoschisin production and retinal layer splitting [1][6][9]. Characterized by macular schisis, reduced visual acuity (typically 20/60–20/120), and peripheral retinal involvement in 40-50% of cases [4][6][12]. Complications include retinal detachment (5-22%) and vitreous hemorrhage [10][19]. Management focuses on carbonic anhydrase inhibitors (e.g., dorzolamide) to reduce schisis cavities, amblyopia treatment, and surgical intervention for complications [8][12][16].
Therapies
Topical/systemic carbonic anhydrase inhibitors (e.g., dorzolamide) improve retinal structure and stabilize vision [12][16]
Vitreoretinal surgery for retinal detachment/vitreous hemorrhage (5-40% require intervention) [10][19]
Investigational gene therapies using subretinal AAV vectors (e.g., Atsena Therapeutics’ AAV.SPR) [3][16][20]
Categories: rare developmental anomalies during embryogenesis, rare genetic diseases, rare ophthalmic disorders
Research Papers
234 drug discovery papers about X-linked retinoschisis, with 1 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
234 drug discovery papers about X-linked retinoschisis, with 1 first-in-class and 5 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-11 | Randomised Clinical Trial to Evaluate the Efficacy of Acetazolamide for the Treatment of Cystoid Fluid Collections in X-Linked Retinoschisis: The AXIS Trial.
This trial aimed to evaluate the efficacy of oral acetazolamide in reducing cystoid fluid collections (CFC) and improving visual function in patients with X-linked retinoschisis (XLRS). In this investigator-initiated, single centre, open-label, randomised controlled trial, XLRS patients aged ≥ 12 years with fovea-involving CFC at baseline were eligible. Participants were randomised 1:1 to receive either oral acetazolamide (500 mg/day for 16 weeks, followed by tapering or discontinuation based on response) or no treatment (control) for 32 weeks. Seven study visits were completed over 32 weeks. The primary outcome was central subfield thickness (CST). Secondary outcomes included functional and structural measures, as well as patient-reported visual disability. A total of 19 patients were enrolled: 10 received acetazolamide (17 eyes), and nine were monitored without treatment (16 eyes). The difference in CST from baseline up to week 32 between the treatment and control groups was on average +2.7 μm (p = 0.9; 95% CI, -68.1 to 73.5 μm). Retinal sensitivity on microperimetry showed a modest statistically significant improvement favouring acetazolamide. However, no significant improvements were observed for best-corrected visual acuity, low-luminance visual acuity, cystoid fluid collection volume or patient-reported visual disability in the treatment group compared to the control group. This study found no clinically meaningful benefit of oral acetazolamide for reducing CFC or improving visual function in the overall XLRS population. Although structural and functional outcomes were comparable between groups overall, a small subset of patients may experience benefit, suggesting a personalised treatment approach may be warranted.
2026-06-05 | Modulation of Systemic Osmolarity Alters Retinal Thickness and Schisis Cavities Without Blood Retinal Barrier Disruption in Rs1 Knockout Mice.
The purpose of this study was to determine whether systemic osmolarity modulation through dehydration or hydration alters retinal thickness and schisis cavity area in Rs1 knockout (KO) mice compared with wild-type (WT) controls, and whether such changes occur without disruption of the blood-retinal barrier (BRB). Postnatal day 30 Rs1 KO and WT mice underwent dehydration (dry anesthesia) or hydration (intraperitoneal injection of distilled water, 40 mL/kg) during in vivo optical coherence tomography (OCT) imaging. Retinal thickness and schisis cavity area were quantified from serial OCT B-scans. BRB integrity was evaluated using fluorescein angiography (FA) and immunostaining of retinal and retinal pigment epithelium (RPE) junctional markers. Dehydration significantly reduced retinal thickness and schisis cavity area in Rs1 KO mice, with changes of greater magnitude than those observed in WT controls. Hydration increased retinal thickness in WT mice, whereas Rs1 KO mice had a relatively blunted and variable structural response compared to WT in both retinal thickness and schisis cavity area. FA and immunostaining revealed no evidence of vascular leakage or RPE junctional disruption in either genotype, indicating preserved BRB integrity under all experimental conditions. These results demonstrate that systemic osmolarity modulation alters retinal structure in X-linked retinoschisis (XLRS) through mechanisms independent of BRB disruption. The exaggerated response to dehydration and attenuated response to hydration in Rs1 KO suggest altered intraretinal fluid dynamics and biomechanical constraints associated with schisis cavities. These findings indicate that modulation of osmolarity may represent a potential therapeutic approach for intraretinal fluid accumulation in XLRS.
2026-01-28 | Microglial phagocytosis of bipolar cells triggers inner retinal degeneration in Rs1-KO mice.
BACKGROUND: X-linked juvenile retinoschisis (XLRS) is a hereditary retinal disorder caused by mutations in the RS1 gene that leads to the formation of cavities in the inner nuclear layer (INL) and progressive vision loss, characterized by a disproportionate reduction of the b-wave compared to the a-wave in electroretinography (ERG). While previous research has largely focused on photoreceptor degeneration in XLRS, the specific roles of other cell populations, particularly bipolar cells and microglia, in the early stages of the disease have remained less well understood. Thus, this study aimed to elucidate the early cellular and molecular mechanisms of retinal degeneration in XLRS, with a particular focus on the role of microglia and bipolar cells. METHODS: Retinal structure and function were assessed in CRISPR/Cas9 Rs1-exon2 knockout (Rs1−/y) mice at 8 and 24 weeks using histology, spectral-domain optical coherence tomography (SD-OCT), ERG, and optokinetic response. To analyze cell-specific changes, we performed TUNEL assay, immunofluorescence, flow cytometry, and single-cell RNA sequencing (scRNA-seq) with trajectory analysis. RESULTS: Rs1−/y mice successfully recapitulated classic XLRS features, including INL schisis, reduced b/a-wave ERG ratio, and early vision loss. TUNEL assay and histological analysis revealed that cell death initiated in the INL at 8 weeks and progressed to the outer nuclear layer (ONL), while microglia displayed a progressive transition from a ramified to an ameboid morphology. scRNA-seq demonstrated a significant loss of cone bipolar cells, especially OFF-cone subtypes, which preceded photoreceptor degeneration. Importantly, microglial activation and enhanced phagocytosis of OFF-cone bipolar cells were observed prior to photoreceptor loss. This phagocytic process was found to be mediated by phosphatidylserine and complement C3b, independent of caspase-3 pathways. CONCLUSIONS: Our findings demonstrate that bipolar cell degeneration, driven by microglial phagocytosis of stressed yet viable OFF-cone bipolar cells, is an early and critical pathological event in XLRS that precedes photoreceptor loss. This process involves "eat-me" signals and complement activation independent of classical apoptosis. These results provide a new perspective on XLRS pathogenesis and suggest that therapeutic strategies targeting bipolar cells and microglial activity could offer promising avenues for early intervention.
2025-11-20 | Case Report: Carbonic anhydrase inhibitor brinzolamide dramatically improved the morphology and also function of a patient with RS1 mutation.
X-linked retinoschisis (XLRS) is an inherited retinal disease caused by mutations in the RS1 gene, which encodes retinoschisin, a protein essential for maintaining the retinal structure during development. Here, we report the therapeutic evidence in a male patient diagnosed with X-linked retinoschisis (XLRS) before and after topical treatment with a carbonic anhydrase inhibitor (CAI), brinzolamide. XLRS-like typical retinal morphology and visual function before treatment and novel improvements gradually from one to 3 months following treatment were observed; then a recurrence of foveal retinoschisis and decreased retinal function occurred because the use of brinzolamide eye drops was disrupted by months-long recurrent upper respiratory tract infections; eventually retinal improvement after resuming brinzolamide were found again, confirming that brinzolamide eye drops could reduce retinoschisis and improve visual acuity. This individualized "dechallenge-rechallenge" evidence chain provides direct supports for the brinzolamide to be the cause in controlling XLRS progression rather than the natural occurring in the course of the disease itself.
2025-09-13 | Treating x-linked retinoschisis with topical dorzolamide: A case report from Jamnagar
Medical Publisher in Delhi, India - IP Innovative Publication Pvt Limited, Medical Journals Publication, Open Access Journals, Print Journals,Indian Journals, Surgery, Microbiology, Anaesthesia, Anatomy Biochemistry Books and Journals, Skills for Employability,Best Journal Publishers-IP Innovative Publication Pvt Limit
cell therapies
2024-08-10 | Early Developmental Characteristics and Features of a Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis.
X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.
2007-12-12 | Retinoschisin (RS1), the protein encoded by the X-linked retinoschisis gene, is anchored to the surface of retinal photoreceptor and bipolar cells through its interactions with a Na/K ATPase-SARM1 complex.
Retinoschisin or RS1 is a discoidin domain-containing protein encoded by the gene responsible for X-linked retinoschisis (XLRS), an early onset macular degeneration characterized by a splitting of the retina. Retinoschisin, expressed and secreted from photoreceptors and bipolar cells as a homo-octameric complex, associates with the surface of these cells where it serves to maintain the cellular organization of the retina and the photoreceptor-bipolar synaptic structure. To gain insight into the role of retinoschisin in retinal cell adhesion and the pathogenesis of XLRS, we have investigated membrane components in retinal extracts that interact with retinoschisin. Unlike the discoidin domain-containing blood coagulation proteins Factor V and Factor VIII, retinoschisin did not bind to phospholipids or retinal lipids reconstituted into unilamellar vesicles or immobilized on microtiter plates. Instead, co-immunoprecipitation studies together with mass spectrometric-based proteomics and Western blotting showed that retinoschisin is associated with a complex consisting of Na/K ATPase (alpha3, beta2 isoforms) and the sterile alpha and TIR motif-containing protein SARM1. Double labeling studies for immunofluorescence microscopy confirmed the co-localization of retinoschisin with Na/K ATPase and SARM1 in photoreceptors and bipolar cells of retina tissue. We conclude that retinoschisin binds to Na/K ATPase on photoreceptor and bipolar cells. This interaction may be part of a novel SARM1-mediated cell signaling pathway required for the maintenance of retinal cell organization and photoreceptor-bipolar synaptic structure.
gene therapies
2026-04-01 | Intrafamilial variability in X-linked retinoschisis: Report of two affected brothers from a large family
X-linked retinoschisis (XLRS) is an inherited retinal dystrophy caused by mutations in the RS1 gene, typically presenting in young males with bilateral foveal schisis and variable peripheral involvement. We report the case of a 25-year-old male, the eighth of ten siblings, who presented with progressive diminution of vision in both eyes over the past 6 months. His best-corrected visual acuity was 6/18 in the right eye and 6/60 in the left eye. Fundus examination showed classical foveal schisis and spectral-domain optical coherence tomography (OCT) confirmed multilayer schitic cavities, more extensive in the left eye. A younger brother also demonstrated OCT-documented bilateral retinoschisis but with better visual acuity, highlighting intrafamilial phenotypic variability. Genetic testing could not be performed due to financial constraints, underscoring the diagnostic challenges in the resource-limited settings where multimodal imaging is indispensable. The proband was started on topical dorzolamide and oral acetazolamide, but no functional or structural improvement has been observed so far. This case contributes to the expanding clinical spectrum of XLRS, emphasizes variability in phenotypic expression within the same family, and illustrates the limitations of current treatment options while pointing toward the potential of emerging gene-based therapies.
2025-10-16 | Dual delivery of supramolecular nanoparticle-carried minicircle donor DNA with Cas9/gRNA improved HITI knock-in efficiency in X-linked juvenile retinoschisis.
X-linked retinoschisis (XLRS) is a hereditary mutation of the RS1 gene and is characterized by early-onset maculopathy with severe visual impairment. Current gene therapy utilizing CRISPR-associated protein 9 (Cas9) is ongoing; however, the optimization of nonviral/nanoparticle CRISPR/Cas9-based therapeutics for gene delivery into nondivided retinal neurons remains undetermined. Minicircles DNA, a circular DNA molecule lacking bacterial backbone sequences, has gained recognition for improving transfection efficiency and biosafety. Here, we developed a supramolecular nanoparticle (SMNP)-editing platform in which SMNPs carrying CRISPR/Cas9 integrated minicircle donor DNA (mc dDNA) to achieve highly efficient and precise gene knock-in. To increase the efficiency of RS1 gene knock-in, we replaced the conventional mc dDNA with a single flanking-Cas9/cut site. Furthermore, using homology-independent targeted integration (HITI) as an editing-nondivided cell strategy, SMNP-carried CRISPR/Cas9 could effectively facilitate the dual delivery of mc-RS1/GFP dDNA and Cas9/gRNA plasmids. Compared with the delivery of the Cas9/gRNA plasmid alone (~20 %), the delivery of mc-RS1/GFP dDNA via SMNPs had significantly higher transfection efficiency (90 %). Further flow cytometry analysis revealed that 5.99 % of the FACS-positive cells were detected in the mc-RS1/GFP dDNA group, markedly exceeding the 2.21 % with long-term expression in the conventional dDNA group. Moreover, when XLRS/iPSC-derived retinal neuron organoids were used as a patient-based disease model, compared with conventional plasmid-based delivery, robust RS1 expression with integration sustained transgene expression in XLRS/iPSC-derived retinal organoids. Collectively, these findings indicated that SMNP-mediated dual delivery of the Cas9/gRNA plasmid and mc-RS1/GFP dDNA substantially enhanced RS1-targeted integration with long-term transgene expression, providing safer and effective gene therapy for the treatment of XLRS.
2025-05-12 | Data Sheet 1_Regional patterns of genetic variants in expanded carrier screening: a next-generation sequencing pilot study in Fujian Province, China.docx
Background This pilot study aimed to characterize the regional distribution of genetic variants associated with autosomal recessive and X-linked recessive (AR/XLR) conditions in Fujian Province, Southeast China, to inform the development of targeted carrier screening programs. Methods An expanded carrier screening (ECS) panel utilizing next-generation sequencing (NGS) technology was designed to analyze 332 genes associated with 343 AR/XLR conditions. The panel was applied to 440 samples obtained from individuals in Fujian Province. Single nucleotide variants and copy number variations (CNVs) were identified and analyzed using a multidimensional approach that incorporated demographic characteristics, carrier frequencies, and the genetic burden of AR/XLR diseases. Results A total of 511 variants were detected among the 440 participants, including 43 CNVs (8.41%), affecting 133 genes associated with 123 conditions. The mean number of pathogenic or likely pathogenic variants per sample was 1.16. The highest genetic burden was observed in couples seeking medically assisted reproduction (MAR group), who had histories of fetal loss, second- or third-trimester abnormalities, or postnatal abnormalities. In clinical settings, the percentage of at-risk couples (ARCs) was 6.36% (n = 14), involving seven conditions, with no statistically significant difference in ARC incidence between couples undergoing genetic screening (GS group) and the MAR group. The cumulative carrier rate for 28 genes was ≥1/100. Recurrent variants in GAA, GALT, CYP1B1, and MEFV were identified, exhibiting distinct regional patterns compared to previously reported variants in the Han Chinese population. Conclusion NGS-based ECS demonstrates significant potential for assessing the genetic burden of AR/XLR conditions and identifying ARCs in Fujian Province. However, before integrating ECS into regional public health initiatives, the development of a region-specific, curated disease panel is necessary to optimize screening efficacy and clinical utility.
2025-04-24 | CRISPR Cas systems: From bacterial defense mechanisms to revolutionary tools reshaping genetic research and translation therapeutics
The CRISPR-Cas systems, initially identified as bacterial defense mechanisms, have become innovative tools for genetic research and translational therapeutics. These systems are made up of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, which precisely target and cleave specific genome sequences, thus providing bacteria with immunity against viral infections. This review traces the evolution of CRISPR-Cas systems from their discovery as a bacterial defence mechanism to present uses in genetic engineering and beyond. The diversity of these systems, their structure and function, and the profound impact of these systems on genetic research, including their use in the creation of novel therapies for a variety of diseases, will be explored. In particular, this review discuss therapeutic applications of CRISPR in various neurodegenerative disorders (Alzheimer disease, Huntington’s disease and Parkinson’s disease), cardiovascular diseases, viral disorders including HIV, blood disorders (β-thalassemia, haemophilia and sickle cell anaemia), ocular disorders (Retinitis pigmentosa, Leber's congenital amaurosis, Aniridia, X-linked juvenile retinoschisis) mitochondrial disorders, Duchene muscular dystrophy and cancer along with the prospects concerning them. Furthermore, we discuss recent advancements, including novel Cas variants (CasΦ, CasX/Cas12f), precision editing technologies (base editing and prime editing), advanced delivery systems (nanoparticles, viral vectors), and emerging diagnostic platforms (SHERLOCK and DETECTR). Despite the extensive literature available on CRISPR-Cas systems, there remains a need for an updated review addressing recent developments, technological advancements, and future directions. This review aims to fill this gap by presenting an in-depth analysis of cutting-edge research, distinguishing itself from previous reviews by incorporating newly discovered CRISPR-Cas variants, emerging therapeutic strategies, and evolving regulatory landscapes.
2025-04-04 | Comparison of retinal structure and schisis location in X-linked retinoschisis and enhanced S-cone syndrome.
To provide a quantitative assessment of the primary retinal layers affected by macular cystoid spaces in X-linked retinoschisis (XLRS) and enhanced S-cone syndrome (ESCS). Twenty-two visually-normal controls, 14 XLRS and 7 ESCS (autosomal recessive inheritance) subjects participated. Macular B-scans were acquired by OCT and the thickness of the inner-nuclear layer (INL), outer-nuclear layer plus outer-plexiform layer (OPL+ONL), and photoreceptor outer segments (OS+) was calculated. ANOVA was used to compare mean thicknesses within each layer for the three subject groups. Thirteen of 14 XLRS subjects and all 7 ESCS subjects had macular schisis by OCT. The INL was significantly thicker than normal for the XLRS group, but not significantly different from normal for the ESCS group. Conversely, the OPL+ONL was abnormally thick for all ESCS subjects and abnormally thin for all XLRS subjects. OS+ was significantly thinned for the XLRS group, but not significantly different from normal for the ESCS group. In this sample of subjects, macular cystoid spaces were most apparent in the INL of XLRS subjects and in the OPL+ONL of ESCS subjects. Additionally, photoreceptor thinning was a characteristic of XLRS, which was less apparent in ESCS. These data provide insight into the location of macular cystoid spaces and highlight anatomical differences between XLRS and ESCS patients.
antibodies
2024-05-30 | Choroidal neovascularisation secondary toX-linked retinoschisis.
Choroidal neovascularisation (CNV) in patients with X-linked retinoschisis (XLRS) has been poorly documented. This study aims to investigate the prevalence and clinical characteristics of CNV in patients with XLRS, as well as analyse the preliminary genotype-phenotype correlation. A retrospective case series of patients with genetically confirmed XLRS was included. Demographic, clinical and genetic features were analysed, with a comparison between CNV and non-CNV eyes. Among 185 eyes of 129 patients with XLRS, the prevalence of CNV was 8.1% (15/185). The mean diagnostic age of all patients with CNV is 5.1±2.56 years. CNV eyes exhibited a mean best-corrected visual acuity (BCVA) (logarithm of the minimal angle of resolution) of 1.37±0.74. All CNVs were classified as subretinal and active. Peripapillary CNVs accounted for 80.0% (12/15), while subfoveal CNVs accounted for 20.0% (3/15). In CNV eyes, the prevalence of macular atrophy (5/15, 33.3%, p=0.013) and bullous peripheral schisis (14/15, 93.3%, p=0.000) was higher compared with non-CNV eyes. Additionally, CNV eyes exhibited poorer integrity of the outer retina and BCVA (p=0.007) compared with non-CNV eyes. All 15 eyes with CNV underwent anti-vascular endothelial growth factor (anti-VEGF) therapy. Genotype analysis revealed that 7 of 10 patients (70.0%, 10 eyes) were predicted to have missense variants, while 3 of 10 patients (30.0%, 5 eyes) exhibited severe variants. The prevalence of CNV in XLRS eyes was found to be 8.1%. All CNVs secondary to XLRS were active and classified as type 2. CNV eyes demonstrated poorer visual function and compromised retinal structures. Anti-VEGF therapy demonstrated effectiveness in treating XLRS-CNVs. No significant genotype-phenotype correlation was established.
2022-12-15 | Retinal vasoproliferative tumor as first sign of X-linked retinoschisis in a 12-month-old boy.
X-linked retinoschisis (XLRS) has been associated with retinal vascular abnormalities, but retinal vasoproliferative tumor (RVPT) has been rarely reported in this context. We describe the case of a 12-month-old boy presenting with esotropia of his left eye due to extensive exudation secondary to RVPT. Right eye examination revealed macular and bullous peripheral retinoschisis. Combining laser photocoagulation and intravitreal injections of anti-vascular endothelial growth factor allowed control of the exudative process at 12 months follow-up. RVPT could be the first sign of XLRS.
2018-03-01 | Retinal vasproliferative tumor in a case of X-linked retinoschisis detachment
To describe the first published case of X-linked retinoschisis (XLRS) detachment with retinal vasoproliferative tumor (RVPT) and provide a literature review of the subject.The authors describe a case of a 17 year old male with X-linked retinoschisis who presented with a retinal detachment and a retinal vasoproliferative tumor. The patient was treated with pars plana vitrectomy, endolaser, subtenon's kenalog and anti-VEGF (vascular endothelial growth factor) intravitreal injections. He regained 20/60 vision with a flat macula and had significant resolution of the associated vasoproliferative leakage seen on fluorescein angiography.This case adds XLRS to the conditions associated with RVPT and gives support for treatment with laser photocoagulation and anti-VEGF therapy with bevacizumab to control the exudative process.
2017-03-08 | Genetic analysis and clinical features of X-linked retinoschisis in Chinese patients
Many mutations in the retinoschisis (RS1) gene have been identified, but there are limited clinical data relating to the different genotypes. This study investigated the genotype, clinical phenotype and therapies for X-linked juvenile retinoschisis (XLRS) patients in China to evaluate the effects of gene mutations and therapies on the prognosis of the disease. Thirty patients were recruited in the study. Genetic examination identified 8 novel RS1 gene mutations. Twenty-four patients were identified as missense mutation, which was the most common gene mutation in XLRS patients. Amino acids 102 and 209 were the most common mutation areas, accounting for a total 35.7% of all patients. Mutations affecting amino acid 102 were associated with poor results on the flash electroretinogram (ERG). Sixteen patients had various complications. Anti-vascular endothelial growth factor (VEGF) drugs were given to four patients with hemorrhage or other complications, and serious adverse events did not occur. Our outcome demonstrates that missense mutation was the leading cause of XLRS and more than half of the patients with this missense had various complications. Anti-VEGF drugs may be an effective and safe way to prevent deterioration of XLRS with certain complications. There is wide genotypic and phenotypic variability in Chinese patients with XLRS.
2015-08-03 | Retinal microglia: just bystander or target for therapy?
Resident microglial cells can be regarded as the immunological watchdogs of the brain and the retina. They are active sensors of their neuronal microenvironment and rapidly respond to various insults with a morphological and functional transformation into reactive phagocytes. There is strong evidence from animal models and in situ analyses of human tissue that microglial reactivity is a common hallmark of various retinal degenerative and inflammatory diseases. These include rare hereditary retinopathies such as retinitis pigmentosa and X-linked juvenile retinoschisis but also comprise more common multifactorial retinal diseases such as age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis as well as neurological disorders with ocular manifestation. In this review, we describe how microglial function is kept in balance under normal conditions by cross-talk with other retinal cells and summarize how microglia respond to different forms of retinal injury. In addition, we present the concept that microglia play a key role in local regulation of complement in the retina and specify aspects of microglial aging relevant for chronic inflammatory processes in the retina. We conclude that this resident immune cell of the retina cannot be simply regarded as bystander of disease but may instead be a potential therapeutic target to be modulated in the treatment of degenerative and inflammatory diseases of the retina.
small molecules
2026-08-11 | Randomised Clinical Trial to Evaluate the Efficacy of Acetazolamide for the Treatment of Cystoid Fluid Collections in X-Linked Retinoschisis: The AXIS Trial.
This trial aimed to evaluate the efficacy of oral acetazolamide in reducing cystoid fluid collections (CFC) and improving visual function in patients with X-linked retinoschisis (XLRS). In this investigator-initiated, single centre, open-label, randomised controlled trial, XLRS patients aged ≥ 12 years with fovea-involving CFC at baseline were eligible. Participants were randomised 1:1 to receive either oral acetazolamide (500 mg/day for 16 weeks, followed by tapering or discontinuation based on response) or no treatment (control) for 32 weeks. Seven study visits were completed over 32 weeks. The primary outcome was central subfield thickness (CST). Secondary outcomes included functional and structural measures, as well as patient-reported visual disability. A total of 19 patients were enrolled: 10 received acetazolamide (17 eyes), and nine were monitored without treatment (16 eyes). The difference in CST from baseline up to week 32 between the treatment and control groups was on average +2.7 μm (p = 0.9; 95% CI, -68.1 to 73.5 μm). Retinal sensitivity on microperimetry showed a modest statistically significant improvement favouring acetazolamide. However, no significant improvements were observed for best-corrected visual acuity, low-luminance visual acuity, cystoid fluid collection volume or patient-reported visual disability in the treatment group compared to the control group. This study found no clinically meaningful benefit of oral acetazolamide for reducing CFC or improving visual function in the overall XLRS population. Although structural and functional outcomes were comparable between groups overall, a small subset of patients may experience benefit, suggesting a personalised treatment approach may be warranted.
2026-06-05 | Modulation of Systemic Osmolarity Alters Retinal Thickness and Schisis Cavities Without Blood Retinal Barrier Disruption in Rs1 Knockout Mice.
The purpose of this study was to determine whether systemic osmolarity modulation through dehydration or hydration alters retinal thickness and schisis cavity area in Rs1 knockout (KO) mice compared with wild-type (WT) controls, and whether such changes occur without disruption of the blood-retinal barrier (BRB). Postnatal day 30 Rs1 KO and WT mice underwent dehydration (dry anesthesia) or hydration (intraperitoneal injection of distilled water, 40 mL/kg) during in vivo optical coherence tomography (OCT) imaging. Retinal thickness and schisis cavity area were quantified from serial OCT B-scans. BRB integrity was evaluated using fluorescein angiography (FA) and immunostaining of retinal and retinal pigment epithelium (RPE) junctional markers. Dehydration significantly reduced retinal thickness and schisis cavity area in Rs1 KO mice, with changes of greater magnitude than those observed in WT controls. Hydration increased retinal thickness in WT mice, whereas Rs1 KO mice had a relatively blunted and variable structural response compared to WT in both retinal thickness and schisis cavity area. FA and immunostaining revealed no evidence of vascular leakage or RPE junctional disruption in either genotype, indicating preserved BRB integrity under all experimental conditions. These results demonstrate that systemic osmolarity modulation alters retinal structure in X-linked retinoschisis (XLRS) through mechanisms independent of BRB disruption. The exaggerated response to dehydration and attenuated response to hydration in Rs1 KO suggest altered intraretinal fluid dynamics and biomechanical constraints associated with schisis cavities. These findings indicate that modulation of osmolarity may represent a potential therapeutic approach for intraretinal fluid accumulation in XLRS.
2026-01-28 | Microglial phagocytosis of bipolar cells triggers inner retinal degeneration in Rs1-KO mice.
BACKGROUND: X-linked juvenile retinoschisis (XLRS) is a hereditary retinal disorder caused by mutations in the RS1 gene that leads to the formation of cavities in the inner nuclear layer (INL) and progressive vision loss, characterized by a disproportionate reduction of the b-wave compared to the a-wave in electroretinography (ERG). While previous research has largely focused on photoreceptor degeneration in XLRS, the specific roles of other cell populations, particularly bipolar cells and microglia, in the early stages of the disease have remained less well understood. Thus, this study aimed to elucidate the early cellular and molecular mechanisms of retinal degeneration in XLRS, with a particular focus on the role of microglia and bipolar cells. METHODS: Retinal structure and function were assessed in CRISPR/Cas9 Rs1-exon2 knockout (Rs1−/y) mice at 8 and 24 weeks using histology, spectral-domain optical coherence tomography (SD-OCT), ERG, and optokinetic response. To analyze cell-specific changes, we performed TUNEL assay, immunofluorescence, flow cytometry, and single-cell RNA sequencing (scRNA-seq) with trajectory analysis. RESULTS: Rs1−/y mice successfully recapitulated classic XLRS features, including INL schisis, reduced b/a-wave ERG ratio, and early vision loss. TUNEL assay and histological analysis revealed that cell death initiated in the INL at 8 weeks and progressed to the outer nuclear layer (ONL), while microglia displayed a progressive transition from a ramified to an ameboid morphology. scRNA-seq demonstrated a significant loss of cone bipolar cells, especially OFF-cone subtypes, which preceded photoreceptor degeneration. Importantly, microglial activation and enhanced phagocytosis of OFF-cone bipolar cells were observed prior to photoreceptor loss. This phagocytic process was found to be mediated by phosphatidylserine and complement C3b, independent of caspase-3 pathways. CONCLUSIONS: Our findings demonstrate that bipolar cell degeneration, driven by microglial phagocytosis of stressed yet viable OFF-cone bipolar cells, is an early and critical pathological event in XLRS that precedes photoreceptor loss. This process involves "eat-me" signals and complement activation independent of classical apoptosis. These results provide a new perspective on XLRS pathogenesis and suggest that therapeutic strategies targeting bipolar cells and microglial activity could offer promising avenues for early intervention.
2025-11-20 | Case Report: Carbonic anhydrase inhibitor brinzolamide dramatically improved the morphology and also function of a patient with RS1 mutation.
X-linked retinoschisis (XLRS) is an inherited retinal disease caused by mutations in the RS1 gene, which encodes retinoschisin, a protein essential for maintaining the retinal structure during development. Here, we report the therapeutic evidence in a male patient diagnosed with X-linked retinoschisis (XLRS) before and after topical treatment with a carbonic anhydrase inhibitor (CAI), brinzolamide. XLRS-like typical retinal morphology and visual function before treatment and novel improvements gradually from one to 3 months following treatment were observed; then a recurrence of foveal retinoschisis and decreased retinal function occurred because the use of brinzolamide eye drops was disrupted by months-long recurrent upper respiratory tract infections; eventually retinal improvement after resuming brinzolamide were found again, confirming that brinzolamide eye drops could reduce retinoschisis and improve visual acuity. This individualized "dechallenge-rechallenge" evidence chain provides direct supports for the brinzolamide to be the cause in controlling XLRS progression rather than the natural occurring in the course of the disease itself.
2025-09-13 | Treating x-linked retinoschisis with topical dorzolamide: A case report from Jamnagar
Medical Publisher in Delhi, India - IP Innovative Publication Pvt Limited, Medical Journals Publication, Open Access Journals, Print Journals,Indian Journals, Surgery, Microbiology, Anaesthesia, Anatomy Biochemistry Books and Journals, Skills for Employability,Best Journal Publishers-IP Innovative Publication Pvt Limit
cell therapies
2024-08-10 | Early Developmental Characteristics and Features of a Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis.
X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.
2007-12-12 | Retinoschisin (RS1), the protein encoded by the X-linked retinoschisis gene, is anchored to the surface of retinal photoreceptor and bipolar cells through its interactions with a Na/K ATPase-SARM1 complex.
Retinoschisin or RS1 is a discoidin domain-containing protein encoded by the gene responsible for X-linked retinoschisis (XLRS), an early onset macular degeneration characterized by a splitting of the retina. Retinoschisin, expressed and secreted from photoreceptors and bipolar cells as a homo-octameric complex, associates with the surface of these cells where it serves to maintain the cellular organization of the retina and the photoreceptor-bipolar synaptic structure. To gain insight into the role of retinoschisin in retinal cell adhesion and the pathogenesis of XLRS, we have investigated membrane components in retinal extracts that interact with retinoschisin. Unlike the discoidin domain-containing blood coagulation proteins Factor V and Factor VIII, retinoschisin did not bind to phospholipids or retinal lipids reconstituted into unilamellar vesicles or immobilized on microtiter plates. Instead, co-immunoprecipitation studies together with mass spectrometric-based proteomics and Western blotting showed that retinoschisin is associated with a complex consisting of Na/K ATPase (alpha3, beta2 isoforms) and the sterile alpha and TIR motif-containing protein SARM1. Double labeling studies for immunofluorescence microscopy confirmed the co-localization of retinoschisin with Na/K ATPase and SARM1 in photoreceptors and bipolar cells of retina tissue. We conclude that retinoschisin binds to Na/K ATPase on photoreceptor and bipolar cells. This interaction may be part of a novel SARM1-mediated cell signaling pathway required for the maintenance of retinal cell organization and photoreceptor-bipolar synaptic structure.
gene therapies
2026-04-01 | Intrafamilial variability in X-linked retinoschisis: Report of two affected brothers from a large family
X-linked retinoschisis (XLRS) is an inherited retinal dystrophy caused by mutations in the RS1 gene, typically presenting in young males with bilateral foveal schisis and variable peripheral involvement. We report the case of a 25-year-old male, the eighth of ten siblings, who presented with progressive diminution of vision in both eyes over the past 6 months. His best-corrected visual acuity was 6/18 in the right eye and 6/60 in the left eye. Fundus examination showed classical foveal schisis and spectral-domain optical coherence tomography (OCT) confirmed multilayer schitic cavities, more extensive in the left eye. A younger brother also demonstrated OCT-documented bilateral retinoschisis but with better visual acuity, highlighting intrafamilial phenotypic variability. Genetic testing could not be performed due to financial constraints, underscoring the diagnostic challenges in the resource-limited settings where multimodal imaging is indispensable. The proband was started on topical dorzolamide and oral acetazolamide, but no functional or structural improvement has been observed so far. This case contributes to the expanding clinical spectrum of XLRS, emphasizes variability in phenotypic expression within the same family, and illustrates the limitations of current treatment options while pointing toward the potential of emerging gene-based therapies.
2025-10-16 | Dual delivery of supramolecular nanoparticle-carried minicircle donor DNA with Cas9/gRNA improved HITI knock-in efficiency in X-linked juvenile retinoschisis.
X-linked retinoschisis (XLRS) is a hereditary mutation of the RS1 gene and is characterized by early-onset maculopathy with severe visual impairment. Current gene therapy utilizing CRISPR-associated protein 9 (Cas9) is ongoing; however, the optimization of nonviral/nanoparticle CRISPR/Cas9-based therapeutics for gene delivery into nondivided retinal neurons remains undetermined. Minicircles DNA, a circular DNA molecule lacking bacterial backbone sequences, has gained recognition for improving transfection efficiency and biosafety. Here, we developed a supramolecular nanoparticle (SMNP)-editing platform in which SMNPs carrying CRISPR/Cas9 integrated minicircle donor DNA (mc dDNA) to achieve highly efficient and precise gene knock-in. To increase the efficiency of RS1 gene knock-in, we replaced the conventional mc dDNA with a single flanking-Cas9/cut site. Furthermore, using homology-independent targeted integration (HITI) as an editing-nondivided cell strategy, SMNP-carried CRISPR/Cas9 could effectively facilitate the dual delivery of mc-RS1/GFP dDNA and Cas9/gRNA plasmids. Compared with the delivery of the Cas9/gRNA plasmid alone (~20 %), the delivery of mc-RS1/GFP dDNA via SMNPs had significantly higher transfection efficiency (90 %). Further flow cytometry analysis revealed that 5.99 % of the FACS-positive cells were detected in the mc-RS1/GFP dDNA group, markedly exceeding the 2.21 % with long-term expression in the conventional dDNA group. Moreover, when XLRS/iPSC-derived retinal neuron organoids were used as a patient-based disease model, compared with conventional plasmid-based delivery, robust RS1 expression with integration sustained transgene expression in XLRS/iPSC-derived retinal organoids. Collectively, these findings indicated that SMNP-mediated dual delivery of the Cas9/gRNA plasmid and mc-RS1/GFP dDNA substantially enhanced RS1-targeted integration with long-term transgene expression, providing safer and effective gene therapy for the treatment of XLRS.
2025-05-12 | Data Sheet 1_Regional patterns of genetic variants in expanded carrier screening: a next-generation sequencing pilot study in Fujian Province, China.docx
Background This pilot study aimed to characterize the regional distribution of genetic variants associated with autosomal recessive and X-linked recessive (AR/XLR) conditions in Fujian Province, Southeast China, to inform the development of targeted carrier screening programs. Methods An expanded carrier screening (ECS) panel utilizing next-generation sequencing (NGS) technology was designed to analyze 332 genes associated with 343 AR/XLR conditions. The panel was applied to 440 samples obtained from individuals in Fujian Province. Single nucleotide variants and copy number variations (CNVs) were identified and analyzed using a multidimensional approach that incorporated demographic characteristics, carrier frequencies, and the genetic burden of AR/XLR diseases. Results A total of 511 variants were detected among the 440 participants, including 43 CNVs (8.41%), affecting 133 genes associated with 123 conditions. The mean number of pathogenic or likely pathogenic variants per sample was 1.16. The highest genetic burden was observed in couples seeking medically assisted reproduction (MAR group), who had histories of fetal loss, second- or third-trimester abnormalities, or postnatal abnormalities. In clinical settings, the percentage of at-risk couples (ARCs) was 6.36% (n = 14), involving seven conditions, with no statistically significant difference in ARC incidence between couples undergoing genetic screening (GS group) and the MAR group. The cumulative carrier rate for 28 genes was ≥1/100. Recurrent variants in GAA, GALT, CYP1B1, and MEFV were identified, exhibiting distinct regional patterns compared to previously reported variants in the Han Chinese population. Conclusion NGS-based ECS demonstrates significant potential for assessing the genetic burden of AR/XLR conditions and identifying ARCs in Fujian Province. However, before integrating ECS into regional public health initiatives, the development of a region-specific, curated disease panel is necessary to optimize screening efficacy and clinical utility.
2025-04-24 | CRISPR Cas systems: From bacterial defense mechanisms to revolutionary tools reshaping genetic research and translation therapeutics
The CRISPR-Cas systems, initially identified as bacterial defense mechanisms, have become innovative tools for genetic research and translational therapeutics. These systems are made up of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, which precisely target and cleave specific genome sequences, thus providing bacteria with immunity against viral infections. This review traces the evolution of CRISPR-Cas systems from their discovery as a bacterial defence mechanism to present uses in genetic engineering and beyond. The diversity of these systems, their structure and function, and the profound impact of these systems on genetic research, including their use in the creation of novel therapies for a variety of diseases, will be explored. In particular, this review discuss therapeutic applications of CRISPR in various neurodegenerative disorders (Alzheimer disease, Huntington’s disease and Parkinson’s disease), cardiovascular diseases, viral disorders including HIV, blood disorders (β-thalassemia, haemophilia and sickle cell anaemia), ocular disorders (Retinitis pigmentosa, Leber's congenital amaurosis, Aniridia, X-linked juvenile retinoschisis) mitochondrial disorders, Duchene muscular dystrophy and cancer along with the prospects concerning them. Furthermore, we discuss recent advancements, including novel Cas variants (CasΦ, CasX/Cas12f), precision editing technologies (base editing and prime editing), advanced delivery systems (nanoparticles, viral vectors), and emerging diagnostic platforms (SHERLOCK and DETECTR). Despite the extensive literature available on CRISPR-Cas systems, there remains a need for an updated review addressing recent developments, technological advancements, and future directions. This review aims to fill this gap by presenting an in-depth analysis of cutting-edge research, distinguishing itself from previous reviews by incorporating newly discovered CRISPR-Cas variants, emerging therapeutic strategies, and evolving regulatory landscapes.
2025-04-04 | Comparison of retinal structure and schisis location in X-linked retinoschisis and enhanced S-cone syndrome.
To provide a quantitative assessment of the primary retinal layers affected by macular cystoid spaces in X-linked retinoschisis (XLRS) and enhanced S-cone syndrome (ESCS). Twenty-two visually-normal controls, 14 XLRS and 7 ESCS (autosomal recessive inheritance) subjects participated. Macular B-scans were acquired by OCT and the thickness of the inner-nuclear layer (INL), outer-nuclear layer plus outer-plexiform layer (OPL+ONL), and photoreceptor outer segments (OS+) was calculated. ANOVA was used to compare mean thicknesses within each layer for the three subject groups. Thirteen of 14 XLRS subjects and all 7 ESCS subjects had macular schisis by OCT. The INL was significantly thicker than normal for the XLRS group, but not significantly different from normal for the ESCS group. Conversely, the OPL+ONL was abnormally thick for all ESCS subjects and abnormally thin for all XLRS subjects. OS+ was significantly thinned for the XLRS group, but not significantly different from normal for the ESCS group. In this sample of subjects, macular cystoid spaces were most apparent in the INL of XLRS subjects and in the OPL+ONL of ESCS subjects. Additionally, photoreceptor thinning was a characteristic of XLRS, which was less apparent in ESCS. These data provide insight into the location of macular cystoid spaces and highlight anatomical differences between XLRS and ESCS patients.
antibodies
2024-05-30 | Choroidal neovascularisation secondary toX-linked retinoschisis.
Choroidal neovascularisation (CNV) in patients with X-linked retinoschisis (XLRS) has been poorly documented. This study aims to investigate the prevalence and clinical characteristics of CNV in patients with XLRS, as well as analyse the preliminary genotype-phenotype correlation. A retrospective case series of patients with genetically confirmed XLRS was included. Demographic, clinical and genetic features were analysed, with a comparison between CNV and non-CNV eyes. Among 185 eyes of 129 patients with XLRS, the prevalence of CNV was 8.1% (15/185). The mean diagnostic age of all patients with CNV is 5.1±2.56 years. CNV eyes exhibited a mean best-corrected visual acuity (BCVA) (logarithm of the minimal angle of resolution) of 1.37±0.74. All CNVs were classified as subretinal and active. Peripapillary CNVs accounted for 80.0% (12/15), while subfoveal CNVs accounted for 20.0% (3/15). In CNV eyes, the prevalence of macular atrophy (5/15, 33.3%, p=0.013) and bullous peripheral schisis (14/15, 93.3%, p=0.000) was higher compared with non-CNV eyes. Additionally, CNV eyes exhibited poorer integrity of the outer retina and BCVA (p=0.007) compared with non-CNV eyes. All 15 eyes with CNV underwent anti-vascular endothelial growth factor (anti-VEGF) therapy. Genotype analysis revealed that 7 of 10 patients (70.0%, 10 eyes) were predicted to have missense variants, while 3 of 10 patients (30.0%, 5 eyes) exhibited severe variants. The prevalence of CNV in XLRS eyes was found to be 8.1%. All CNVs secondary to XLRS were active and classified as type 2. CNV eyes demonstrated poorer visual function and compromised retinal structures. Anti-VEGF therapy demonstrated effectiveness in treating XLRS-CNVs. No significant genotype-phenotype correlation was established.
2022-12-15 | Retinal vasoproliferative tumor as first sign of X-linked retinoschisis in a 12-month-old boy.
X-linked retinoschisis (XLRS) has been associated with retinal vascular abnormalities, but retinal vasoproliferative tumor (RVPT) has been rarely reported in this context. We describe the case of a 12-month-old boy presenting with esotropia of his left eye due to extensive exudation secondary to RVPT. Right eye examination revealed macular and bullous peripheral retinoschisis. Combining laser photocoagulation and intravitreal injections of anti-vascular endothelial growth factor allowed control of the exudative process at 12 months follow-up. RVPT could be the first sign of XLRS.
2018-03-01 | Retinal vasproliferative tumor in a case of X-linked retinoschisis detachment
To describe the first published case of X-linked retinoschisis (XLRS) detachment with retinal vasoproliferative tumor (RVPT) and provide a literature review of the subject.The authors describe a case of a 17 year old male with X-linked retinoschisis who presented with a retinal detachment and a retinal vasoproliferative tumor. The patient was treated with pars plana vitrectomy, endolaser, subtenon's kenalog and anti-VEGF (vascular endothelial growth factor) intravitreal injections. He regained 20/60 vision with a flat macula and had significant resolution of the associated vasoproliferative leakage seen on fluorescein angiography.This case adds XLRS to the conditions associated with RVPT and gives support for treatment with laser photocoagulation and anti-VEGF therapy with bevacizumab to control the exudative process.
2017-03-08 | Genetic analysis and clinical features of X-linked retinoschisis in Chinese patients
Many mutations in the retinoschisis (RS1) gene have been identified, but there are limited clinical data relating to the different genotypes. This study investigated the genotype, clinical phenotype and therapies for X-linked juvenile retinoschisis (XLRS) patients in China to evaluate the effects of gene mutations and therapies on the prognosis of the disease. Thirty patients were recruited in the study. Genetic examination identified 8 novel RS1 gene mutations. Twenty-four patients were identified as missense mutation, which was the most common gene mutation in XLRS patients. Amino acids 102 and 209 were the most common mutation areas, accounting for a total 35.7% of all patients. Mutations affecting amino acid 102 were associated with poor results on the flash electroretinogram (ERG). Sixteen patients had various complications. Anti-vascular endothelial growth factor (VEGF) drugs were given to four patients with hemorrhage or other complications, and serious adverse events did not occur. Our outcome demonstrates that missense mutation was the leading cause of XLRS and more than half of the patients with this missense had various complications. Anti-VEGF drugs may be an effective and safe way to prevent deterioration of XLRS with certain complications. There is wide genotypic and phenotypic variability in Chinese patients with XLRS.
2015-08-03 | Retinal microglia: just bystander or target for therapy?
Resident microglial cells can be regarded as the immunological watchdogs of the brain and the retina. They are active sensors of their neuronal microenvironment and rapidly respond to various insults with a morphological and functional transformation into reactive phagocytes. There is strong evidence from animal models and in situ analyses of human tissue that microglial reactivity is a common hallmark of various retinal degenerative and inflammatory diseases. These include rare hereditary retinopathies such as retinitis pigmentosa and X-linked juvenile retinoschisis but also comprise more common multifactorial retinal diseases such as age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis as well as neurological disorders with ocular manifestation. In this review, we describe how microglial function is kept in balance under normal conditions by cross-talk with other retinal cells and summarize how microglia respond to different forms of retinal injury. In addition, we present the concept that microglia play a key role in local regulation of complement in the retina and specify aspects of microglial aging relevant for chronic inflammatory processes in the retina. We conclude that this resident immune cell of the retina cannot be simply regarded as bystander of disease but may instead be a potential therapeutic target to be modulated in the treatment of degenerative and inflammatory diseases of the retina.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
8 orphan drug designations for X-linked retinoschisis.
8 orphan drug designations for X-linked retinoschisis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Adeno-associated viral vector serotype 44.9 containing the human HRS1 gene | gene therapies | EMA | 2026-02-23 | — | Asphalion S.L. |
Recombinant adeno-associated virus 8 (AAV8) expressing human retinoschisin (RS1) gene | gene therapies | FDA | 2024-10-22 | — | Chengdu Genevector Biotechnology Co., Ltd. |
Engineered adeno-associated virus spreading capsid encapsulating a human retinoschisin (hRS1) transgene | gene therapies | FDA | 2024-08-21 | — | Atsena Therapeutics, Inc. |
Modified Recombinant adeno-associated virus (rAAV) serotype 2 vector, AAV.IVT18, expressing human retinoschisis gene RS1 driven by RS1 and CMV chimeric promoter | gene therapies | FDA | 2024-02-08 | — | InnoVec Biotherapeutics Inc. |
Recombinant adeno-associated virus (rAAV) vector expressing human retinoschisis protein RS1 | gene therapies | FDA | 2022-11-15 | — | Langxin Qisheng (Suzhou) Biopharmaceutical Co., Ltd. |
adeno-associated virus type 8 delivering a vector genome with human retinoschisin promoter (RS/IRBP) and the human retinoschisin cDNA (hRS) | gene therapies | FDA | 2015-11-16 | — | VegaVect, Inc. |
Recombinant adeno-associated viral vector containing the human retinoschisin gene | gene therapies | EMA | 2013-03-12 | — | Propharma Group The Netherlands B.V. |
adeno-associated viral vector expressing human retinoschisin-1 gene | gene therapies | FDA | 2007-05-21 | — | TeamedOn International, Inc. |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.