Search Results (258)

Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited retinal degenerative disorders characterized by progressive photoreceptor loss and vision impairment, for which broadly applicable mutation-independent therapies remain limited. To examine the therapeutic potential of combined galanin receptor 3 (GALR3) inhibition and antioxidant therapy in a mutation-independent context, we utilized the rd10 mouse model of RP. We first evaluated the effects of individual treatments with the GALR3 antagonist SNAP-37889 and the antioxidant quercetin, followed by a combined treatment regimen to determine whether simultaneous targeting of neuroinflammatory and oxidative stress pathways provides enhanced retinal protection. Treatment efficacy was assessed using functional and morphological analyses, including electroretinography (ERG) to measure retinal function, optical coherence tomography (OCT) to evaluate retinal structure in vivo, and histological and immunohistochemical analyses to quantify photoreceptor survival and markers of retinal oxidative stress and inflammation. Although the expression levels of individual inflammatory and oxidative stress markers did not consistently exhibit additive responses, the combined treatment produced greater photoreceptor survival and preservation of photopic retinal function than either monotherapy alone. These findings support the hypothesis that simultaneous modulation of oxidative stress and neuroinflammation provides greater neuroprotective benefits, establish a foundation for the development of mutation-independent therapeutic strategies for RP, and identify GALR3 as a promising therapeutic target. Full article

Full-field stimulus threshold (FST) testing is a psychophysical method used to assess global retinal function, particularly in patients with severe visual impairment where conventional perimetry is unreliable. This review explores the development, clinical protocols, and applications of FST in retinal diseases, with a focus on its role in inherited retinal dystrophies (IRDs) such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). FST has emerged as a key functional outcome measure in clinical trials, particularly in evaluating novel gene therapies for IRDs. Its fixation-independent nature and ability to detect residual visual function make it valuable for assessing disease progression and treatment efficacy. However, challenges remain regarding standardization and test variability. Ongoing efforts seek to standardize and optimize FST protocols and establish it as a standardized metric in both clinical and research settings. Full article

Retinitis pigmentosa (RP) is a rare inherited retinal disorder in which fundus changes may be subtle and heterogeneous, limiting detection from color fundus images. This study evaluated multiple machine learning architectures for binary-RP versus healthy-control classification, and developed a reproducible pipeline for research-oriented screening support. Three publicly available fundus datasets were combined, including 248 RP images and 1045 healthy controls. An 80/20 train–test split was used, with targeted data augmentation applied only to RP images in the training set to address class imbalance. ConvNeXt-Tiny, ResNet101V2, EfficientNet-B0, a baseline classifier, and custom shallow convolutional neural networks were compared using accuracy, precision, recall, F1-score, confusion matrices, and ROC/precision–recall analyses. A compact ShallowCNN provided the best sensitivity–performance trade-off. On the fixed image-level test set, Adam with a learning rate of 0.0005 reached 96.51% accuracy, while SGD with a learning rate of 0.001 achieved 98% RP recall, minimizing false negatives. The trained models were exported to ONNX and integrated into a Windows inference tool. The proposed framework provides an open, reproducible benchmark for technical evaluation, although external validation is required before clinical use. Full article

Background: To assess how historical patterns in retinitis pigmentosa (RP) gene inheritance, functional category, and phenotypic onset may inform the remaining unsolved RP discovery space. Methods: We manually reviewed PubMed-indexed primary reports in the RetiGene database, supplemented with PubMed-indexed human studies where necessary to improve extractable phenotype data. Gene-level variables extracted included age of symptom onset, inheritance pattern, functional category and syndromic association. Gene-level associations between earliest year of RP gene discovery and mean age of symptom onset were assessed, alongside temporal analyses for functional category, inheritance, and syndromic patterns. Results: Later year of gene discovery was associated with later mean age of symptom onset, both in the primary analysis restricted to genes with at least 5 extractable onset cases (n = 83, p < 0.001) and in a stricter sensitivity analysis restricted to genes with at least 10 onset cases (n = 66, p = 0.00525). Year of discovery differed significantly across functional categories (p < 0.001). No significant temporal association was observed for AR versus non-AR inheritance or syndromic status. Conclusions: This hypothesis-generating analysis suggests that observed patterns likely reflect a combination of biological detectability, study design, and publication dynamics rather than intrinsic gene–phenotype relationships alone; within this context, future RP-solving efforts may benefit from greater attention to less obvious biological pathways (such as ciliary, transport, and metabolic categories), along with later-presenting or less conspicuous phenotypes. Full article

Purpose: We aimed to compare the volume of the lateral geniculate nucleus (LGN) in patients with different stages of retinitis pigmentosa (RP) with regard to age, sex and symmetry of the LGN. Methods: The investigated cohort included 13 patients with moderate (median Snellen visual acuity 0.75) and 18 patients with advanced (median Snellen visual acuity 0.06) RP-related visual field loss. The volumes of the left and right LGNs were manually measured using ITK-SNAP software after an examination of the brain with a 7 Tesla MRI. A linear mixed statistical model was used to assess LGN volume regarding age and gender of moderate and advanced RP patients and symmetry of both LGNs. Results: The mixed-effects linear model did not reveal a significant effect of disease group on LGN volume after adjusting for age and sex (F(1.27) = 0.01, p = 0.91). A significant effect of the LGN side was demonstrated, with the volume of the right LGN being significantly greater than that of the left (F(1.29) = 29.45, p < 0.001) in both disease groups, left–right. The interaction between disease group and LGN side was not statistically significant (F(1.29) = 0.45, p = 0.51). There is a tendency for LGN to decrease with age (F(1.27) = 3.84, p = 0.060), and there is no gender predilection (F(1.27) = 0.11, p = 0.74) in RP patients. There was correlation found between left LGN volume and visual acuity (ρ = 0.64) and central retinal thickness (ρ = 0.71) in the moderate group). Conclusions: No significant differences in LGN volume were found between patients with moderate and advanced RP. Furthermore, the volume of the right LGN was larger than the volume of the left LGN in RP patients, and this asymmetry is not gender-dependent. Correlation was found between the left LGN volume and visual acuity and central retinal thickness in moderate group. Our findings may have clinical implications for future RP management. Full article

Background and Clinical Significance: Biallelic pathogenic variants in the PCARE gene (photoreceptor cilium actin regulator), also known as C2orf71 (chromosome 2 open reading frame 71), are typically associated with retinitis pigmentosa type 54 (RP54) and, less frequently, with cone–rod dystrophy (CORD23). Case Presentation: A 52-year-old man presented with an eight-year history of progressive visual loss, without photophobia or nyctalopia. He underwent a comprehensive ophthalmological evaluation, including multimodal retinal imaging, automated perimetry, and full electrophysiological testing, in accordance with International Society for Clinical Electrophysiology of Vision (ISCEV)’s standards. Genetic testing was performed using next-generation sequencing (NGS) with an inherited retinal dystrophy gene panel, and findings were confirmed by Sanger sequencing. Clinical examination revealed bilateral macular atrophy with minimal foveal sparing and a central scotoma. Optical coherence tomography (OCT) showed disruption of the outer retinal layers and retinal pigment epithelium (RPE) abnormalities. Fundus autofluorescence (FAF) demonstrated central hypoautofluorescence surrounded by a hyperautofluorescent ring. Electrophysiological testing revealed severely reduced rod- and cone- mediated responses on full-field electroretinography (ERG), absent pattern ERG responses, and markedly reduced multifocal ERG responses, indicating widespread retinal dysfunction with significant macular involvement. Genetic analysis identified a homozygous pathogenic nonsense variant in PCARE [c.3289C>T; p.(Gln1097*)], confirming the diagnosis of an autosomal recessive inherited retinal dystrophy. Conclusions: Biallelic PCARE variants can cause late-onset severe retinal dystrophy, with predominant macular involvement and cone–rod dysfunction. Given its phenotypic overlap with other inherited retinal diseases, accurate diagnosis requires the integration of multimodal retinal imaging, electrophysiological testing, and comprehensive genetic analysis. Full article

Optogenetic gene therapy-based treatment offers a unique approach to bypass dysfunctional or degenerated photoreceptors in retinal degenerative disorders. Ambient light-activatable multi-characteristic opsin (MCO) targeted to bipolar cells of the retina has demonstrated partial vision restoration in animal models of retinitis pigmentosa (RP). Here, we describe the potential therapeutic efficacy of intravitreally delivered AAV-carried MCO-010 in a mouse model of Stargardt disease. MCO-010 treatment led to significantly improved behavioral outcomes in the visually guided radial arm water maze. Furthermore, longitudinal optical coherence tomographic imaging showed that the MCO-010 treatment led to no notable change in the retina thickness. Furthermore, the MCO-010-treated mice exhibited higher electrophysiological responses compared to the control group. Together, these findings demonstrate potential vision-restoring and disease-modifying aspects of ambient light-activatable intravitreal MCO-010 therapy. Full article

Background/Objectives: Retinitis pigmentosa (RP) is characterized by progressive degeneration of photoreceptors, with increasing evidence supporting the involvement of inflammation in disease progression. Aqueous humor (AH) reflects the intraocular microenvironment and represents an accessible source for biochemical analysis. This study aimed to characterize the profile of the main inflammatory proteins and bioactive lipids in the AH of RP patients and to compare it with healthy subjects. Methods: The AH was analyzed for cytokines using multiplex immunoassays and for lipid species using liquid chromatography–mass spectrometry. The concentrations of the analyzed molecules were compared between RP patients and the control group and then correlated with age and ellipsoid zone (EZ) width in RP patients. Results: A total of 26 RP patients and 13 controls were recruited. Significantly elevated levels of the pro-inflammatory IL-6 and a significant decrease in vascular endothelial growth factor (VEGF) were found in RP patients compared to controls. In RP patients, lipidomic analysis demonstrated significant increases in medium- and long-chain sphingomyelins (SMs) and very-long-chain unsaturated phosphatidylcholines (PCs). Higher levels of Cer 16:0, PC 32:0, and PC 34:0 were significantly associated with greater EZ preservation in RP patients. Additionally, in RP patients, VEGF and GM-CSF levels increased significantly with age, while IL-8 showed a non-significant decreasing trend. Conclusions: By integrating proteomic and, for the first time, lipidomic analyses of AH, we identified significant alterations in pro-inflammatory cytokines and bioactive lipid species in RP patients compared to controls, further highlighting a link between inflammatory activity, patient age, and disease stage. These preliminary findings need further validation in larger longitudinal cohorts to confirm the clinical utility of these bioactive mediators as potential disease biomarkers. Full article

Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited retinal degenerations with primary degeneration of rod photoreceptors followed by secondary cone loss. We investigated whether downregulating Nrl (neural retina leucine zipper), a key transcription factor specifying rod fate, can reprogram rods into a more resilient state. In a transgenic Nrl^N/N mouse in which Nrl was markedly downregulated, the rod phenotype became more like a rod precursor, particularly in the inferior retina. Crossing Nrl^N/N mice with two rod degeneration models, rd1 (Pde6b^rd1/rd1) and rhodopsin P23H knock-in (Rho^P23H/P23H) mice, showed significantly improved photoreceptor survival in double-mutant mice. In addition, AAV-mediated delivery of shRNA targeting Nrl mRNA substantially enhanced photoreceptor survival in rd10 (Pde6b^rd10/rd10) mice. These findings demonstrate that downregulation of Nrl reprograms rods and confers broad resistance to degeneration across multiple RP models. AAV-mediated Nrl knockdown represents a promising mutation-independent therapeutic strategy for autosomal recessive and dominant forms of RP. Full article

Inherited retinal dystrophies (IRDs) comprise a diverse group of genetic disorders that frequently result in irreversible vision loss due to photoreceptor dysfunction or degeneration. Among them, retinitis pigmentosa (RP) and achromatopsia (ACHM) are, in some cases, associated with pathogenic variants in PDE6A and PDE6C, respectively, which are key components of the phototransduction cascade. As most of IRDs still lack effective therapies, retinal organoids (ROs) provide a valuable in vitro model for the investigation of disease-associated mechanisms. Here, we generated induced pluripotent stem cell (iPSC)-derived ROs from an RP patient carrying compound heterozygous PDE6A mutations and from a patient with ACHM harboring a homozygous PDE6C mutation, along with their corresponding CRISPR/Cas9-corrected isogenic controls, which, to our knowledge, represent the first patient-derived RO models reported for the PDE6A and PDE6C genes. The mutant PDE6A line exhibited impaired neuroretinal vesicle formation and RO differentiation; however, a subset of RP-derived ROs matured appropriately and retained photoreceptor features. Moreover, the specific isoform expression pattern detected in retinal tissues reflected differences across developmental maturation stages that could influence disease severity. In contrast, the PDE6C_mutant ROs displayed normal structure and maturation, although cGMP hydrolysis within photoreceptors was likely compromised. In both models, CRISPR/Cas9-mediated correction restored the disease-associated phenotype resembling wild-type ROs. Collectively, these findings provide new insights into PDE6-associated pathogenesis, underscore the utility of patient-specific and gene-corrected ROs for elucidating IRD mechanisms, and support gene editing as a promising therapeutic strategy. Full article

Purpose: To evaluate the safety and feasibility of repeated subtenon administration of autologous platelet-rich plasma (PRP) in patients with degenerative retinal diseases and to explore preliminary, hypothesis-generating functional observations in retinitis pigmentosa (RP) and extensive macular atrophy with pseudodrusen-like appearance (EMAP). Methods: This prospective, open-label, uncontrolled pilot study included 13 patients (6 RP, 7 EMAP) who received three subtenon PRP injections (1.5 mL each) at baseline, Month 2, and Month 4, with follow-up through Month 6. The study was designed primarily to assess safety and feasibility and was not powered or intended to evaluate efficacy. The primary outcome was safety, including adverse events and intraocular pressure changes. Exploratory secondary outcomes included best-corrected visual acuity (BCVA, logMAR), visual field mean deviation (MD), and structural optical coherence tomography (OCT) parameters. Electrophysiological outcomes were analyzed descriptively due to incomplete paired data. Analyses were conducted within diagnostic groups, and no between-group comparisons were performed. Results: All 13 patients completed the study. No serious adverse events or permanent ocular morbidity were observed. Two transient and self-limited adverse events occurred (anterior uveitis and intraocular pressure elevation), both resolving without sequelae. In the overall cohort, BCVA remained stable without statistically significant change. In the RP subgroup, a small exploratory change in BCVA was observed (mean ΔlogMAR −0.09; nominal p = 0.048), corresponding to approximately 4–5 ETDRS letters; however, this finding was associated with wide confidence intervals and limited statistical power and should be interpreted cautiously. In the EMAP subgroup, functional stability was observed without evidence of consistent improvement. Visual field mean deviation and OCT findings were consistent with absence of short-term deterioration across available paired data. Electrophysiological outcomes showed no consistent directional change. Conclusions: Repeated subtenon PRP administration appeared feasible and well tolerated in this small, uncontrolled pilot cohort. Any observed functional changes are preliminary and hypothesis-generating only and do not establish efficacy. Larger, adequately powered controlled studies with standardized endpoints are required to determine the potential role of PRP in degenerative retinal diseases. Full article

Background: Non-syndromic retinitis pigmentosa (RP) is characterized by rod–cone degeneration, resulting in night blindness, visual field constriction, and eventual blindness. Recessively inherited RP is predominantly exacerbated in consanguineous populations, such as Pakistan. This study aimed to perform the genetic analysis of sixteen non-syndromic RP segregating Pakistani families, and to summarize the mutation spectrum of non-syndromic RP in our population by reviewing related literature. Methods: We screened 16 non-syndromic RP families using targeted capture panel sequencing of 344 genes related to inherited retinal dystrophies. Variants were prioritized based on rarity (minor allele frequency (MAF) < 0.001 in the gnomAD South Asian subset), pathogenicity assessments using ACMG/AMP criteria, and REVEL scores (>0.5). Candidate variants were validated for familial segregation through Sanger sequencing. Results: We identified 15 distinct variants across 14 genes associated with non-syndromic retinitis pigmentosa, comprising 6 missense, 7 nonsense, 1 frameshift, and 2 splice-site variants, including 4 novel variants, i.e., p.(Val220Met) and p.(Pro1282SerfsTer2) in RP1, 1 each in PDE6B (c.2021+5G>A), and PRCD p.(Ser38Ter). Homozygosity predominated, underscoring the impact of consanguinity on the burden of autosomal recessive disease in the present cohort, while the CERKL disease-causing mutation, i.e., p.(Arg257Ter), recurred in two families. Conclusions: This study expands Pakistan’s non-syndromic RP mutational spectrum by identifying novel variants in RP1, PDE6B, and PRCD, alongside recurrent CERKL and RHO mutations of the local population. The literature review suggests that RP1, TULP1, and PDE6B are among the most mutated genes in our population, supporting the value of population-specific genetic panels to enhance diagnostics and carrier screening. Full article

Coenzyme Q10 (CoQ10), a natural antioxidant produced by the human body, has strong anti-inflammatory properties, reduces oxidative stress, and improves mitochondrial function. It is also known for its strong neuroprotective effects. With age, endogenously produced CoQ10 levels decline, contributing to the development of chronic diseases, including eye disorders. Irreversible ocular diseases that result in blindness present a significant challenge in contemporary medicine, as no fully effective cure exists; current treatments primarily aim to decelerate disease progression, manage symptoms, and preserve residual vision. Our study reviews research on the use of CoQ10 in eye diseases like age-related macular degeneration (AMD), retinitis pigmentosa (RP), and glaucoma, which can cause permanent vision loss and are linked to oxidative stress and mitochondrial dysfunction. This article explores whether CoQ10 can be a safe and effective addition to treatment for these conditions. We also outline directions for future research and explain how CoQ10 functions in the studies discussed in this review. Full article

Background/Objectives: To describe retinal imaging characteristics and the natural history of rhodopsin (RHO)-associated autosomal dominant retinitis pigmentosa (ADRP) by evaluating ellipsoid zone (EZ) width loss and measuring the degree of constriction of the area within and including the hyperautofluorescent ring. Methods: Eighteen patients with molecularly confirmed RHO variants were retrospectively evaluated. EZ width on spectral-domain optical coherence tomography (SD-OCT) and the area within and including the hyperfluorescent ring on fundus autofluorescence (FAF) were measured. The correlation between EZ width and hyperfluorescent ring area was assessed using a linear mixed-effects model. Results: Mean best corrected visual acuity (BCVA) (logMAR) was 0.21 at baseline and 0.29 at last visit over a mean follow-up of 5 years. Nine patients presented with sectoral RP, eight with typical RP, and one with unilateral RP. The mean EZ width constriction rate was −93.43 µm/year (SD = 130.58), and the area within and including the hyperautofluorescent ring decreased by −0.54 mm²/year (SD = 0.50). A strong positive association was observed between the EZ width and hyperfluorescent ring area at baseline (β = 151.7 ± 17.9, p < 0.001) and at the final visit (β = 185.7 ± 18.2, p < 0.001). Conclusions: In this study, patients with RHO-associated ADRP appeared to show a relatively slow rate of progression. Quantitative imaging markers, such as EZ width and the area within and including the hyperautofluorescent ring, may offer potentially reproducible measures of disease progression. These imaging biomarkers could be useful as outcome measures in future natural history studies and therapeutic trials, pending further validation. Full article

Fibroblast growth factor 2 (FGF2) is expressed in retinal Müller glia cells, and its expression increases in response to photoreceptor degeneration. To investigate the physiological relevance of FGF2, we analyzed retinal morphology and cellular responses in Fgf2-deficient (Fgf2^−/−) mice. Loss of FGF2 did not affect photoreceptor survival, retinal vasculature, or retinal pigment epithelium (RPE) integrity. To further understand its role in retinal degeneration, Fgf2^−/− mice were crossed with Pde6b^STOP/STOP mice, a model of retinitis pigmentosa (RP). We then analyzed outer nuclear layer thickness, cone number, rod outer segments length, RPE morphology, and microglia number in Fgf2^−/− Pde6b^STOP/STOP and Pde6b^STOP/STOP mice. Although FGF2 was upregulated in degenerating photoreceptor cells in the Pde6b^STOP/STOP retina, its absence did not accelerate photoreceptor loss in Fgf2^−/− Pde6b^STOP/STOP mice. Interestingly, microglia numbers were significantly changed at early disease stages in Fgf2^−/− Pde6b^STOP/STOP retinas compared with Pde6b^STOP/STOP controls, suggesting that FGF2 modulates inflammatory signaling. Together, these results show that loss of FGF2 does not alter photoreceptor degeneration kinetics or retinal morphology, but may contribute to the regulation of early microglial accumulation during degeneration. Full article