RARE DISEASE
Fundus albipunctatus
Fundus albipunctatus
Fundus albipunctatus
Drug discovery
0
drugs
With orphan designations
Overview
Fundus albipunctatus is a rare autosomal recessive retinal dystrophy characterized by congenital stationary night blindness, delayed dark adaptation, and distinct whitish-yellow retinal flecks sparing the macula. Primarily linked to RDH5 mutations disrupting the visual cycle, it occasionally involves LRAT or RPE65 genes. While typically stable, some patients develop progressive macular degeneration or cone dysfunction later in life [1][2][4][6][8]. Electroretinography reveals impaired scotopic responses improving with prolonged dark adaptation [5][8][12].
Categories: rare genetic diseases, rare ophthalmic disorders
Research Papers
20 drug discovery papers about Fundus albipunctatus, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
20 drug discovery papers about Fundus albipunctatus, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-02-13 | Fundus albipunctatus disease-associated RDH5/L310delinsEV mutation undertakes AMFR-mediated polyubiquitination and degradation in proteasome.
Genetic mutations in retinol dehydrogenase 5 (RDH5) are associated with the inherited autosomal recessive retinal degeneration diseases, especially fundus albipunctatus (FA). Most of RDH5 mutants exhibit downregulation of RDH5 protein expression. However, the regulatory mechanism remains unclear. Here, we studied the metabolism of RDH5/L310delinsEV mutation, an indel mutation closely associated with the inherited FA disease. The half-life of RDH5/L310delinsEV was much less than RDH5/WT. Unlike RDH5/WT, which normally underwent degradation in autophagy-lysosomes, the RDH5/L310delinsEV reduced its location to the endoplasmic reticulum and was easy to be polyubiquitinated and degraded in the ubiquitin-proteasome pathway. Both RDH5/WT and RDH5/L310delinsEV interacted with autocrine motility factor receptor (AMFR), which is an E3 ligase on the endoplasmic reticulum. Overexpression of or knockdown of AMFR by siRNA increased or reduced the degradation of RDH5/L310delinsEV. The lysine 179 and lysine 263 of RDH5/L310delinsEV protein were polyubiquitination sites by AMFR. Mutation of K179R and K263R in RDH5/L310delinsEV protein reduced AMFR-mediated polyubiquitination and degradation. Taken together, these results highlight that RDH5/L310delinsEV mutant in RDH5 causes a rapid degradation in the ubiquitin-proteasome pathway. The fast degradation of RDH5/L310delinsEV may be associated with the FA development.
2025-12-01 | Mechanisms and Functions of Chromophore Regeneration in the Classical Visual Cycle: Implications for Retinal Disease Pathogenesis and Therapy
11-cis-retinal, the indispensable chromophore of photoreceptor opsins, is fundamental for light detection and the initiation of visual signal transduction. Its synthesis and regeneration through the visual cycle are critical not only for phototransduction but also for maintaining retinal homeostasis. Disruption of key enzymes, such as retinal pigment epithelium (RPE)65 and retinol dehydrogenases, results in toxic retinoid accumulation, oxidative stress, and progressive photoreceptor degeneration. These pathological mechanisms contribute to inherited and acquired retinal diseases, including Stargardt disease type 1, age-related macular degeneration, Leber congenital amaurosis, retinitis pigmentosa, and fundus albipunctatus. Recent therapeutic advances, ranging from gene replacement therapy with RPE65 (voretigene neparvovec, Luxturna®) to small-molecule modulators and antioxidant strategies, underscore the translational potential of targeting chromophore metabolism. This review outlines molecular processes underlying chromophore synthesis and regeneration, elucidates how disruptions in these processes contribute to inherited and acquired retinal pathologies, and evaluates existing and emerging therapeutic strategies that target chromophore metabolism. We highlight ongoing challenges and critical knowledge gaps to guide future investigations on basic science, translational research, and clinical practice. This review provides a comprehensive overview of the molecular mechanisms, current therapeutic approaches, and outstanding challenges, with a focus on future intervention directions.
2024-12-27 | HSP90 stabilizes visual cycle retinol dehydrogenase 5 in the endoplasmic reticulum by inhibiting its degradation during autophagy.
Genetic mutations in retinol dehydrogenase 5 (RDH5), a rate-limiting enzyme of the visual cycle, is associated with nyctalopia, age-related macular disease, and stationary congenital fundus albipunctatus (FA). A majority of these mutations impair RDH5 protein expression and intracellular localization. However, the regulatory mechanisms underlying RDH5 metabolism remain unclear. Here, we find that RDH5 undergoes degradation via the autophagy-lysosomal pathway, and its stability is regulated by interacting with HSP90. Deletion of HSP90α or HSP90β by CRISPR-Cas9 or inhibition of HSP90 activity by IPI-504 downregulates RDH5 protein level, but not its mRNA expression, and this downregulation is restored by autophagic inhibitors (3-MA, CQ, and Baf-A1) and siRNA of ATG5 or ATG7, but not by the proteasome inhibitor MG132. RDH5 can physically interact with SQSTM1/P62, and this interaction is enhanced in HSP90-deficient cells as well as in CQ-treated cells. Knocking down SQSTM1/P62 by siRNA induces RDH5 protein accumulation. Moreover, HSP90, RDH5, and Calnexin form a complex through intermolecular interactions. Deficiency of HSP90α or HSP90β dissociates RDH5 from Calnexin and increases RDH5 translocation from the endoplasmic reticulum to the cytosol. Taken together, we propose that dysfunction of HSP90 leads to RDH5 release from Calnexin in the endoplasmic reticulum into the cytosol, where it binds to the adaptor SQSTM1/P62 for degradation in the autolysosome. RDH5 is a novel client candidate of HSP90. The downregulation of RDH5 may be responsible for the nyctalopia side effect noted in cancer patients receiving HSP90 inhibitor treatment currently in the clinical trial.
2023-06-19 | One-Year Outcomes of Oral Treatment With Alga Capsules Containing Low Levels of 9-cis-β-Carotene in RDH5-Related Fundus Albipunctatus
PurposeThis study aimed to clarify the effect of 1-year oral treatment with 9-cis-β-carotene-rich alga Dunaliella Bardawil (Dunaliella supplementation) using full-field electroretinography (ERG) in patients with RDH5-related fundus albipunctatus (FAP).DesignProspective interventional case seriesParticipantsThe study included 12 patients (23 eyes) with RDH5-related FAP.MethodsTwelve patients (23 eyes) with RDH5-related FAP received Dunaliella supplementation (total daily dose of β-carotene was 74.0 mg, comprising 28.4 mg 9-cis-β-carotene and 45.6 mg all-trans-β-carotene at a ratio of 1:1.6) for 1 year and underwent ophthalmic examinations, including full-field ERG at baseline, 3 months, and 1 year after the initial treatment.Main Outcome MeasuresThe main outcome was changes in the amplitudes of responses of full-field ERG before and after treatment. A linear mixed-effects model was used to evaluate the adjusted mean difference between the amplitude of each response pre-treatment and post-treatment.ResultsProlonged dark adapted (DA) responses at 3 months revealed a significant impairment in the b-wave of DA 0.01 (adjusted mean difference; −34.7, 95% CI; −66.8 to −2.73, p = 0.041) and a-wave of DA 3.0 (−29.0, 95% CI; −50.6 to −7.41, p = 0.013) and DA10.0 (−40.4, 95% CI; −67.8 to −13.0, p = 0.007), which were also observed at 1 year. Additionally, prolonged DA and light adapted (LA) responses revealed statistically significant impairment at 1 year in the b-wave of DA 3.0 (−43.8, 95% CI; −82.9 to −4.78, p = 0.035), DA 10.0 (−59.7, 95% CI; −101.8 to −17.61, p = 0.009), LA 3.0 (−7.31, 95% CI; −13.6 to −1.04, p = 0.029), and in LA 3.0 flicker (−7.53, 95% CI; −12.7 to −2.34, p = 0.007).ConclusionsOur study results suggest that Dunaliella supplementation comprising low levels of 9-cis-β-carotene compared with those reported in a previous study (1:1 ratio) adversely affects ERG amplitudes in patients with RDH5-related FAP.
2019-11-01 | Long-term treatment with 9-cis-β-carotene rich alga Dunaliella bardawil ameliorates photoreceptor degeneration in a mouse model of retinoid cycle defect
The retinoid cycle is the enzymatic pathway that regenerates the vision chromophore, 11-cis retinal, after it is bleached during light absorption. Genetic insults to this cycle result in incurable blinding retinal dystrophies such as retinitis pigmentosa and Leber congenital amaurosis. Previous studies demonstrated that oral treatment with 9-cis-β-carotene rich Dunaliella bardawil powder significantly improved visual and retinal function in patients with fundus albipunctatus night blindness and retinitis pigmentosa. Here we examined the effect of oral treatment with the Dunaliella powder on retinal function and structure in RPE65rd12 mice, a model of a genetic defect in the retinoid cycle. Mice were fed with a control diet, vitamin A deficient diet (VAD) or VAD diet supplemented with Dunaliella powder for 13 months. Mice fed with Dunaliella presented significantly higher dark-adapted (35.7 μV ± 3.1 vs. 6.9 μV ± 2.5, p < 0.001 for VAD and vs. 4.3 μV ± 1.1, p < 0.001 for control) and light-adapted (35.1 μV ± 4.3 vs. 6.2 μV ± 3.0, p < 0.001 for VAD and vs. 4.9 μV ± 1.3, p < 0.001 for control) maximal electroretinogram a-wave amplitudes. The Dunaliella group also presented higher dark- and light-adapted maximal electroretinogram b-wave amplitudes compared with the control diet (86.5 μV ± 9.4 vs. 28.7 μV ± 6.3, p < 0.001 and 79.2 μV ± 10.4 vs. 28.3 μV ± 4.7, p = 0.001, respectively), but comparable results to the VAD group. A significantly higher number of M-cone photoreceptors was identified in the retinas of DUNA treated mice. Taken together, our study suggests that 9CBC-rich Dunaliella bardawil powder may present an effective treatment for retinal dystrophies caused by defects in the retinoid cycle.
gene therapies
2026-01-01 | Flecked Retina with Early Onset Nyctalopia in an Adult (Conference e-Poster presentation - College of Ophthalmologists Sri Lanka - 2022)
This Figshare entry presents the original e-poster titled “Presentation of a Case of Flecked Retina in an Adult with Nyctalopia”, which was presented at the 30th Annual Scientific Congress of the College of Ophthalmologists of Sri Lanka (COSL) 2022, held from 22–23 October 2022 in Colombo.The case describes a 45-year-old male with lifelong nyctalopia, peripheral visual field reduction, and preserved central visual acuity (OD 6/6, OS 6/9). Fundus examination revealed widespread yellow-white retinal flecks with relative macular sparing.Clinical evaluation was supported by multimodal retinal imaging, including colour fundus photography, fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT). Functional assessment was performed using ISCEV-standard visual electrophysiology, including full-field ERG under standard and extended dark adaptation protocols, and pattern ERG (PERG).Electrophysiological testing demonstrated generalised rod system dysfunction with associated cone involvement, with no improvement following prolonged (3hrs) dark adaptation, supporting localisation to a diffuse retinal dysfunction within the flecked retina / fundus albipunctatus spectrum. Diagnostic conclusions were therefore based on clinical, imaging, and functional findings.No genetic results were included in the original e-poster, and none are presented in this Figshare main entry. This record preserves the original academic scope and context of the conference presentation.An extended mini-publication incorporating molecular genetic findings is planned as a future output, integrating clinical, imaging, electrophysiological, and genetic data to provide a comprehensive phenotype–genotype correlation.
2024-10-22 | Clinical and Genetic Characteristics of Patients with Peripheral Retinal Flecks in Koreans.
To describe the clinical and genetic features of Korean patients with peripheral retinal flecks unrelated to aging. A retrospective analysis was conducted on the clinical characteristics of patients with symmetric peripheral retinal flecks. Age-related deposits such as reticular pseudodrusen were excluded, as well as secondary deposits related to intraocular inflammation, tumor, and drug toxicity. Multimodal imaging, electrophysiological examinations, and genetic testing were analyzed. A total of 10 patients (two men and eight women) with bilateral peripheral flecks were enrolled in this study. A mean age at diagnosis was 30.5 ± 19.6 years (range, 4-59 years). Within the 10 patients, six were genetically confirmed with monogenic retinal disorders. Biallelic pathogenic variants in RDH5 were found in five patients, and one patient was diagnosed with retinopathy related to Alport syndrome due to a pathogenic variant in COL4A5. Although not genetically confirmed, one case associated with nanophthalmos and another case showing chorioretinal mottling in a carrier of ocular albinism have been identified. In one patient, genetic testing also revealed unknown causes. The mean logarithm of the minimum angle of resolution initial visual acuity was 0.12 ± 0.18 and 0.07 ± 0.18 in right and left eyes, respectively. Night blindness was reported by four patients (40%), with three showing decreased or delayed rod response in electroretinogram, particularly those with RDH5 mutations. Differences in the deposit layers and the patterns of flecks were observed on multimodal imaging. In the study population, we observed various causes and clinical differences in the retinal fleck patterns among Koreans, including RDH5-related fundus albipunctatus and Alport syndrome. Despite reports of night blindness symptoms in some cases, all patients demonstrated satisfactory corrected visual acuity.
2015-03-04 | Adiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival
Abstract The identification of pathways necessary for photoreceptor and retinal pigment epithelium (RPE) function is critical to uncover therapies for blindness. Here we report the discovery of adiponectin receptor 1 (AdipoR1) as a regulator of these cells’ functions. Docosahexaenoic acid (DHA) is avidly retained in photoreceptors, while mechanisms controlling DHA uptake and retention are unknown. Thus, we demonstrate that AdipoR1 ablation results in DHA reduction. In situ hybridization reveals photoreceptor and RPE cell AdipoR1 expression, blunted in AdipoR1 −/− mice. We also find decreased photoreceptor-specific phosphatidylcholine containing very long-chain polyunsaturated fatty acids and severely attenuated electroretinograms. These changes precede progressive photoreceptor degeneration in AdipoR1 −/− mice. RPE-rich eyecup cultures from AdipoR1 −/− reveal impaired DHA uptake. AdipoR1 overexpression in RPE cells enhances DHA uptake, whereas AdipoR1 silencing has the opposite effect. These results establish AdipoR1 as a regulatory switch of DHA uptake, retention, conservation and elongation in photoreceptors and RPE, thus preserving photoreceptor cell integrity.
2012-05-02 | A Homozygous Frameshift Mutation in LRAT Causes Retinitis Punctata Albescens
To determine the genetic defect and to describe the clinical characteristics in patients with retinitis punctata albescens (RPA) and fundus albipunctatus (FAP).Case series/observational study.We included 13 patients affected by RPA or FAP.Thirteen patients were collected from 8 families with a retinal dystrophy characterized by tiny, yellow-white dots on funduscopy, typical for FAP or RPA. All patients underwent full ophthalmologic examinations, including visual field assessment. Fundus photography, and electroretinography were performed in 12 patients, and optical coherence tomography and fundus autofluorescence were performed in 4 patients. DNA samples of all patients were screened for mutations in RLBP1 and for mutations in RDH5 in patients who did not carry mutations in RLBP1. DNA samples of 2 sibling pairs of nonconsanguineous families who carried mutations neither in RLBP1 nor in RDH5 were analyzed by genome-wide homozygosity mapping. Sequence analysis was performed of LRAT, a candidate gene in a shared homozygous region.We assessed DNA sequence variants, best-corrected visual acuity, fundus appearance, visual field measurements, electroretinogram responses, optical coherence tomography, and fundus autofluorescence.A homozygous frameshift mutation was identified in LRAT in 4 patients with RPA. Mutations in RLBP1 were identified in 7 patients with RPA and in 1 patient with FAP and cone dystrophy. One patient had compound heterozygous mutations in RDH5 and suffered from FAP with mild maculopathy.A genetic defect was identified in LRAT as a novel cause of RPA. LRAT is therefore the fourth gene involved in the visual cycle that may cause a white-dot retinopathy. We also revealed that mutations in RLBP1 may lead to FAP with cone dystrophy.
small molecules
2026-02-13 | Fundus albipunctatus disease-associated RDH5/L310delinsEV mutation undertakes AMFR-mediated polyubiquitination and degradation in proteasome.
Genetic mutations in retinol dehydrogenase 5 (RDH5) are associated with the inherited autosomal recessive retinal degeneration diseases, especially fundus albipunctatus (FA). Most of RDH5 mutants exhibit downregulation of RDH5 protein expression. However, the regulatory mechanism remains unclear. Here, we studied the metabolism of RDH5/L310delinsEV mutation, an indel mutation closely associated with the inherited FA disease. The half-life of RDH5/L310delinsEV was much less than RDH5/WT. Unlike RDH5/WT, which normally underwent degradation in autophagy-lysosomes, the RDH5/L310delinsEV reduced its location to the endoplasmic reticulum and was easy to be polyubiquitinated and degraded in the ubiquitin-proteasome pathway. Both RDH5/WT and RDH5/L310delinsEV interacted with autocrine motility factor receptor (AMFR), which is an E3 ligase on the endoplasmic reticulum. Overexpression of or knockdown of AMFR by siRNA increased or reduced the degradation of RDH5/L310delinsEV. The lysine 179 and lysine 263 of RDH5/L310delinsEV protein were polyubiquitination sites by AMFR. Mutation of K179R and K263R in RDH5/L310delinsEV protein reduced AMFR-mediated polyubiquitination and degradation. Taken together, these results highlight that RDH5/L310delinsEV mutant in RDH5 causes a rapid degradation in the ubiquitin-proteasome pathway. The fast degradation of RDH5/L310delinsEV may be associated with the FA development.
2025-12-01 | Mechanisms and Functions of Chromophore Regeneration in the Classical Visual Cycle: Implications for Retinal Disease Pathogenesis and Therapy
11-cis-retinal, the indispensable chromophore of photoreceptor opsins, is fundamental for light detection and the initiation of visual signal transduction. Its synthesis and regeneration through the visual cycle are critical not only for phototransduction but also for maintaining retinal homeostasis. Disruption of key enzymes, such as retinal pigment epithelium (RPE)65 and retinol dehydrogenases, results in toxic retinoid accumulation, oxidative stress, and progressive photoreceptor degeneration. These pathological mechanisms contribute to inherited and acquired retinal diseases, including Stargardt disease type 1, age-related macular degeneration, Leber congenital amaurosis, retinitis pigmentosa, and fundus albipunctatus. Recent therapeutic advances, ranging from gene replacement therapy with RPE65 (voretigene neparvovec, Luxturna®) to small-molecule modulators and antioxidant strategies, underscore the translational potential of targeting chromophore metabolism. This review outlines molecular processes underlying chromophore synthesis and regeneration, elucidates how disruptions in these processes contribute to inherited and acquired retinal pathologies, and evaluates existing and emerging therapeutic strategies that target chromophore metabolism. We highlight ongoing challenges and critical knowledge gaps to guide future investigations on basic science, translational research, and clinical practice. This review provides a comprehensive overview of the molecular mechanisms, current therapeutic approaches, and outstanding challenges, with a focus on future intervention directions.
2024-12-27 | HSP90 stabilizes visual cycle retinol dehydrogenase 5 in the endoplasmic reticulum by inhibiting its degradation during autophagy.
Genetic mutations in retinol dehydrogenase 5 (RDH5), a rate-limiting enzyme of the visual cycle, is associated with nyctalopia, age-related macular disease, and stationary congenital fundus albipunctatus (FA). A majority of these mutations impair RDH5 protein expression and intracellular localization. However, the regulatory mechanisms underlying RDH5 metabolism remain unclear. Here, we find that RDH5 undergoes degradation via the autophagy-lysosomal pathway, and its stability is regulated by interacting with HSP90. Deletion of HSP90α or HSP90β by CRISPR-Cas9 or inhibition of HSP90 activity by IPI-504 downregulates RDH5 protein level, but not its mRNA expression, and this downregulation is restored by autophagic inhibitors (3-MA, CQ, and Baf-A1) and siRNA of ATG5 or ATG7, but not by the proteasome inhibitor MG132. RDH5 can physically interact with SQSTM1/P62, and this interaction is enhanced in HSP90-deficient cells as well as in CQ-treated cells. Knocking down SQSTM1/P62 by siRNA induces RDH5 protein accumulation. Moreover, HSP90, RDH5, and Calnexin form a complex through intermolecular interactions. Deficiency of HSP90α or HSP90β dissociates RDH5 from Calnexin and increases RDH5 translocation from the endoplasmic reticulum to the cytosol. Taken together, we propose that dysfunction of HSP90 leads to RDH5 release from Calnexin in the endoplasmic reticulum into the cytosol, where it binds to the adaptor SQSTM1/P62 for degradation in the autolysosome. RDH5 is a novel client candidate of HSP90. The downregulation of RDH5 may be responsible for the nyctalopia side effect noted in cancer patients receiving HSP90 inhibitor treatment currently in the clinical trial.
2023-06-19 | One-Year Outcomes of Oral Treatment With Alga Capsules Containing Low Levels of 9-cis-β-Carotene in RDH5-Related Fundus Albipunctatus
PurposeThis study aimed to clarify the effect of 1-year oral treatment with 9-cis-β-carotene-rich alga Dunaliella Bardawil (Dunaliella supplementation) using full-field electroretinography (ERG) in patients with RDH5-related fundus albipunctatus (FAP).DesignProspective interventional case seriesParticipantsThe study included 12 patients (23 eyes) with RDH5-related FAP.MethodsTwelve patients (23 eyes) with RDH5-related FAP received Dunaliella supplementation (total daily dose of β-carotene was 74.0 mg, comprising 28.4 mg 9-cis-β-carotene and 45.6 mg all-trans-β-carotene at a ratio of 1:1.6) for 1 year and underwent ophthalmic examinations, including full-field ERG at baseline, 3 months, and 1 year after the initial treatment.Main Outcome MeasuresThe main outcome was changes in the amplitudes of responses of full-field ERG before and after treatment. A linear mixed-effects model was used to evaluate the adjusted mean difference between the amplitude of each response pre-treatment and post-treatment.ResultsProlonged dark adapted (DA) responses at 3 months revealed a significant impairment in the b-wave of DA 0.01 (adjusted mean difference; −34.7, 95% CI; −66.8 to −2.73, p = 0.041) and a-wave of DA 3.0 (−29.0, 95% CI; −50.6 to −7.41, p = 0.013) and DA10.0 (−40.4, 95% CI; −67.8 to −13.0, p = 0.007), which were also observed at 1 year. Additionally, prolonged DA and light adapted (LA) responses revealed statistically significant impairment at 1 year in the b-wave of DA 3.0 (−43.8, 95% CI; −82.9 to −4.78, p = 0.035), DA 10.0 (−59.7, 95% CI; −101.8 to −17.61, p = 0.009), LA 3.0 (−7.31, 95% CI; −13.6 to −1.04, p = 0.029), and in LA 3.0 flicker (−7.53, 95% CI; −12.7 to −2.34, p = 0.007).ConclusionsOur study results suggest that Dunaliella supplementation comprising low levels of 9-cis-β-carotene compared with those reported in a previous study (1:1 ratio) adversely affects ERG amplitudes in patients with RDH5-related FAP.
2019-11-01 | Long-term treatment with 9-cis-β-carotene rich alga Dunaliella bardawil ameliorates photoreceptor degeneration in a mouse model of retinoid cycle defect
The retinoid cycle is the enzymatic pathway that regenerates the vision chromophore, 11-cis retinal, after it is bleached during light absorption. Genetic insults to this cycle result in incurable blinding retinal dystrophies such as retinitis pigmentosa and Leber congenital amaurosis. Previous studies demonstrated that oral treatment with 9-cis-β-carotene rich Dunaliella bardawil powder significantly improved visual and retinal function in patients with fundus albipunctatus night blindness and retinitis pigmentosa. Here we examined the effect of oral treatment with the Dunaliella powder on retinal function and structure in RPE65rd12 mice, a model of a genetic defect in the retinoid cycle. Mice were fed with a control diet, vitamin A deficient diet (VAD) or VAD diet supplemented with Dunaliella powder for 13 months. Mice fed with Dunaliella presented significantly higher dark-adapted (35.7 μV ± 3.1 vs. 6.9 μV ± 2.5, p < 0.001 for VAD and vs. 4.3 μV ± 1.1, p < 0.001 for control) and light-adapted (35.1 μV ± 4.3 vs. 6.2 μV ± 3.0, p < 0.001 for VAD and vs. 4.9 μV ± 1.3, p < 0.001 for control) maximal electroretinogram a-wave amplitudes. The Dunaliella group also presented higher dark- and light-adapted maximal electroretinogram b-wave amplitudes compared with the control diet (86.5 μV ± 9.4 vs. 28.7 μV ± 6.3, p < 0.001 and 79.2 μV ± 10.4 vs. 28.3 μV ± 4.7, p = 0.001, respectively), but comparable results to the VAD group. A significantly higher number of M-cone photoreceptors was identified in the retinas of DUNA treated mice. Taken together, our study suggests that 9CBC-rich Dunaliella bardawil powder may present an effective treatment for retinal dystrophies caused by defects in the retinoid cycle.
gene therapies
2026-01-01 | Flecked Retina with Early Onset Nyctalopia in an Adult (Conference e-Poster presentation - College of Ophthalmologists Sri Lanka - 2022)
This Figshare entry presents the original e-poster titled “Presentation of a Case of Flecked Retina in an Adult with Nyctalopia”, which was presented at the 30th Annual Scientific Congress of the College of Ophthalmologists of Sri Lanka (COSL) 2022, held from 22–23 October 2022 in Colombo.The case describes a 45-year-old male with lifelong nyctalopia, peripheral visual field reduction, and preserved central visual acuity (OD 6/6, OS 6/9). Fundus examination revealed widespread yellow-white retinal flecks with relative macular sparing.Clinical evaluation was supported by multimodal retinal imaging, including colour fundus photography, fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT). Functional assessment was performed using ISCEV-standard visual electrophysiology, including full-field ERG under standard and extended dark adaptation protocols, and pattern ERG (PERG).Electrophysiological testing demonstrated generalised rod system dysfunction with associated cone involvement, with no improvement following prolonged (3hrs) dark adaptation, supporting localisation to a diffuse retinal dysfunction within the flecked retina / fundus albipunctatus spectrum. Diagnostic conclusions were therefore based on clinical, imaging, and functional findings.No genetic results were included in the original e-poster, and none are presented in this Figshare main entry. This record preserves the original academic scope and context of the conference presentation.An extended mini-publication incorporating molecular genetic findings is planned as a future output, integrating clinical, imaging, electrophysiological, and genetic data to provide a comprehensive phenotype–genotype correlation.
2024-10-22 | Clinical and Genetic Characteristics of Patients with Peripheral Retinal Flecks in Koreans.
To describe the clinical and genetic features of Korean patients with peripheral retinal flecks unrelated to aging. A retrospective analysis was conducted on the clinical characteristics of patients with symmetric peripheral retinal flecks. Age-related deposits such as reticular pseudodrusen were excluded, as well as secondary deposits related to intraocular inflammation, tumor, and drug toxicity. Multimodal imaging, electrophysiological examinations, and genetic testing were analyzed. A total of 10 patients (two men and eight women) with bilateral peripheral flecks were enrolled in this study. A mean age at diagnosis was 30.5 ± 19.6 years (range, 4-59 years). Within the 10 patients, six were genetically confirmed with monogenic retinal disorders. Biallelic pathogenic variants in RDH5 were found in five patients, and one patient was diagnosed with retinopathy related to Alport syndrome due to a pathogenic variant in COL4A5. Although not genetically confirmed, one case associated with nanophthalmos and another case showing chorioretinal mottling in a carrier of ocular albinism have been identified. In one patient, genetic testing also revealed unknown causes. The mean logarithm of the minimum angle of resolution initial visual acuity was 0.12 ± 0.18 and 0.07 ± 0.18 in right and left eyes, respectively. Night blindness was reported by four patients (40%), with three showing decreased or delayed rod response in electroretinogram, particularly those with RDH5 mutations. Differences in the deposit layers and the patterns of flecks were observed on multimodal imaging. In the study population, we observed various causes and clinical differences in the retinal fleck patterns among Koreans, including RDH5-related fundus albipunctatus and Alport syndrome. Despite reports of night blindness symptoms in some cases, all patients demonstrated satisfactory corrected visual acuity.
2015-03-04 | Adiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival
Abstract The identification of pathways necessary for photoreceptor and retinal pigment epithelium (RPE) function is critical to uncover therapies for blindness. Here we report the discovery of adiponectin receptor 1 (AdipoR1) as a regulator of these cells’ functions. Docosahexaenoic acid (DHA) is avidly retained in photoreceptors, while mechanisms controlling DHA uptake and retention are unknown. Thus, we demonstrate that AdipoR1 ablation results in DHA reduction. In situ hybridization reveals photoreceptor and RPE cell AdipoR1 expression, blunted in AdipoR1 −/− mice. We also find decreased photoreceptor-specific phosphatidylcholine containing very long-chain polyunsaturated fatty acids and severely attenuated electroretinograms. These changes precede progressive photoreceptor degeneration in AdipoR1 −/− mice. RPE-rich eyecup cultures from AdipoR1 −/− reveal impaired DHA uptake. AdipoR1 overexpression in RPE cells enhances DHA uptake, whereas AdipoR1 silencing has the opposite effect. These results establish AdipoR1 as a regulatory switch of DHA uptake, retention, conservation and elongation in photoreceptors and RPE, thus preserving photoreceptor cell integrity.
2012-05-02 | A Homozygous Frameshift Mutation in LRAT Causes Retinitis Punctata Albescens
To determine the genetic defect and to describe the clinical characteristics in patients with retinitis punctata albescens (RPA) and fundus albipunctatus (FAP).Case series/observational study.We included 13 patients affected by RPA or FAP.Thirteen patients were collected from 8 families with a retinal dystrophy characterized by tiny, yellow-white dots on funduscopy, typical for FAP or RPA. All patients underwent full ophthalmologic examinations, including visual field assessment. Fundus photography, and electroretinography were performed in 12 patients, and optical coherence tomography and fundus autofluorescence were performed in 4 patients. DNA samples of all patients were screened for mutations in RLBP1 and for mutations in RDH5 in patients who did not carry mutations in RLBP1. DNA samples of 2 sibling pairs of nonconsanguineous families who carried mutations neither in RLBP1 nor in RDH5 were analyzed by genome-wide homozygosity mapping. Sequence analysis was performed of LRAT, a candidate gene in a shared homozygous region.We assessed DNA sequence variants, best-corrected visual acuity, fundus appearance, visual field measurements, electroretinogram responses, optical coherence tomography, and fundus autofluorescence.A homozygous frameshift mutation was identified in LRAT in 4 patients with RPA. Mutations in RLBP1 were identified in 7 patients with RPA and in 1 patient with FAP and cone dystrophy. One patient had compound heterozygous mutations in RDH5 and suffered from FAP with mild maculopathy.A genetic defect was identified in LRAT as a novel cause of RPA. LRAT is therefore the fourth gene involved in the visual cycle that may cause a white-dot retinopathy. We also revealed that mutations in RLBP1 may lead to FAP with cone dystrophy.
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