Search Results (217)

The retina is highly sensitive to oxygen and blood supply, and hypoxia plays a key role in retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Müller glial cells, which are essential for retinal homeostasis, respond to injury and hypoxia with reactive gliosis, characterized by the upregulation of the glial fibrillary acidic protein (GFAP) and vimentin, cellular hypertrophy, and extracellular matrix changes, which can impair retinal function and repair. The retinal pigment epithelium (RPE) supports photoreceptors, forms part of the blood–retinal barrier, and protects against oxidative stress; its dysfunction contributes to retinal degenerative diseases such as AMD, retinitis pigmentosa (RP), and Stargardt disease (SD). Extracellular vesicles (EVs) play a crucial role in intercellular communication, protein homeostasis, and immune modulation, and have emerged as promising diagnostic and therapeutic tools. Understanding the role of extracellular vesicles’ (EVs’) signaling machinery of glial cells and the retinal pigment epithelium (RPE) is critical for developing effective treatments for retinal degeneration. In this study, we investigated the bidirectional EV-mediated crosstalk between RPE and Müller cells under hypoxic conditions and its impact on cellular metabolism and retinal cell integrity. Our findings demonstrate that RPE-derived extracellular vesicles (RPE EVs) induce time-dependent metabolic reprogramming in Müller cells. Short-term exposure (24 h) promotes pathways supporting neurotransmitter cycling, calcium and mineral absorption, and glutamate metabolism, while prolonged exposure (72 h) shifts Müller cell metabolism toward enhanced mitochondrial function and ATP production. Conversely, Müller cell-derived EVs under hypoxia influenced RPE metabolic pathways, enhancing fatty acid metabolism, intracellular vesicular trafficking, and the biosynthesis of mitochondrial co-factors such as ubiquinone. Proteomic analysis revealed significant modulation of key regulatory proteins. In Müller cells, hypoxic RPE-EV exposure led to reduced expression of Dyskerin Pseudouridine Synthase 1 (DKc1), Eukaryotic Translation Termination Factor 1 (ETF1), and Protein Ser/Thr phosphatases (PPP2R1B), suggesting alterations in RNA processing, translational fidelity, and signaling. RPE cells exposed to hypoxic Müller cell EVs exhibited elevated Ribosome-binding protein 1 (RRBP1), RAC1/2, and Guanine Nucleotide-Binding Protein G(i) Subunit Alpha-1 (GNAI1), supporting enhanced endoplasmic reticulum (ER) function and cytoskeletal remodeling. Functional assays also revealed the compromised barrier integrity of the outer blood–retinal barrier (oBRB) under hypoxic co-culture conditions. These results underscore the adaptive but time-sensitive nature of retinal cell communication via EVs in response to hypoxia. Targeting this crosstalk may offer novel therapeutic strategies to preserve retinal structure and function in ischemic retinopathies. Full article

Visual field (VF) testing remains a cornerstone in assessing retinal function by measuring how well different parts of the retina detect light. It is essential for early detection, monitoring, and management of many retinal diseases. By mapping retinal sensitivity, VF exams can reveal functional loss before structural changes become visible. This review summarizes how VF testing is applied across key conditions: hydroxychloroquine (HCQ) retinopathy, age-related macular degeneration (AMD), diabetic retinopathy (DR) and macular edema (DME), and inherited disorders including inherited dystrophies such as retinitis pigmentosa (RP). Traditional methods like the Goldmann kinetic perimetry and simple tools such as the Amsler grid help identify large or central VF defects. Automated perimetry (e.g., Humphrey Field Analyzer) provides detailed, quantitative data critical for detecting subtle paracentral scotomas in HCQ retinopathy and central vision loss in AMD. Frequency-doubling technology (FDT) reveals early neural deficits in DR before blood vessel changes appear. Microperimetry offers precise, localized sensitivity maps for macular diseases. Despite its value, VF testing faces challenges including patient fatigue, variability in responses, and interpretation of unreliable results. Recent advances in artificial intelligence, virtual reality perimetry, and home-based perimetry systems are improving test accuracy, accessibility, and patient engagement. Integrating VF exams with these emerging technologies promises more personalized care, earlier intervention, and better long-term outcomes for patients with retinal disease. Full article

Background/Objectives: Senior-Loken syndrome (SLS) is a rare autosomal recessive renal–retinal disease caused by mutations in 10 genes. This study aimed to review the ophthalmic findings, renal function, and genotypes of Korean SLS cases. Methods: We retrospectively reviewed 17 genetically confirmed SLS patients in Korea, including 9 newly identified cases and 8 previously reported. Comprehensive ophthalmologic evaluations and renal assessments were conducted. Genetic testing was performed using whole-genome sequencing (WGS), whole-exome sequencing (WES), or Sanger sequencing. Results: Among the 17 patients, patients with NPHP1 mutations were most common (35.3%), followed by those with NPHP4 (29.4%), IQCB1 (NPHP5, 29.4%), and SDCCAG8 (NPHP10, 5.9%) mutations. Patients with NPHP1 mutations showed retinitis pigmentosa (RP) sine pigmento and preserved central vision independent of renal deterioration. Patients with NPHP4 mutations showed early renal dysfunction. Two patients aged under 20 maintained relatively good visual function, but older individuals progressed to severe retinopathy. Patients with IQCB1 mutations were generally prone to early and severe retinal degeneration, typically manifesting as Leber congenital amaurosis (LCA) (three patients), while two patients exhibited milder RP sine pigmento with preserved central vision. Notably, two out of five (40.0%) maintained normal renal function at the time of diagnosis, and both had large deletions in IQCB1. The patient with SDCCAG8 mutation exhibited both end-stage renal disease and congenital blindness due to LCA. Wide-field fundus autofluorescence (AF) revealed perifoveal and peripapillary hypoAF with a perifoveal hyperAF in younger patients across genotypes. Patients under 20 years old showed relatively preserved central vision, regardless of the underlying genetic mutation. Conclusions: The clinical manifestation of renal and ocular impairment demonstrated heterogeneity among Korean SLS patients according to causative genes, and the severity of renal dysfunction and visual decline was not correlated. Therefore, simultaneous comprehensive evaluations of both renal and ocular function should be performed at the initial diagnosis to guide timely intervention and optimize long-term outcomes. Full article

Degenerative retinal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), are the leading causes of vision loss worldwide. Inflammation plays a crucial role in the pathogenesis of these diseases, with cytokines acting as key mediators of neuroinflammation, vascular dysfunction, and cellular degeneration. This review explores the complex role of cytokines in degenerative retinal diseases, highlighting their involvement in disease progression, cellular interactions, and potential therapeutic strategies. Understanding the cytokine network within the retina may provide novel insights into targeted interventions for these debilitating conditions. Full article

To compare the clinical characteristics of inherited retinal diseases (IRDs) caused by biallelic versus monoallelic variants in the RP1, BEST1, and PROM1 genes. A total of 52 patients (26 female) with genetically confirmed IRDs were retrospectively selected from the records of the Harkness Eye Institute Clinical Coordinating Center at Columbia University Irving Medical Center. In RP1, 3 individuals with biallelic variants and 22 patients with monoallelic variants classified as pathogenic or likely pathogenic were selected. In BEST1, eight individuals with biallelic variants and nine individuals with monoallelic variants classified as either pathogenic or likely pathogenic were included. In PROM1, four individuals with biallelic variants and six patients with monoallelic variants classified as pathogenic or likely pathogenic were selected. All patients underwent multimodal retinal imaging and, when available, full-field electroretinography (ffERG). In all three genes, individuals with biallelic variants had markedly earlier disease onset and more severe phenotypes. In RP1, on SD-OCT, foveal involvement was observed in all biallelic cases (3/3, 100%) and in 4/22 (18%) monoallelic cases. In BEST1, the average age of onset in the biallelic cohort was 7.12 years, and the average age was 32.7 years in the monoallelic cohort. Four of eight (50%) patients in the biallelic group were additionally found to have widespread serous lesions outside of the central macula. This finding was not observed in the monoallelic group. Three of eight (38%) biallelic BEST1 patients had moderate reductions in their photopic flicker. All monoallelic BEST1 patients had photopic responses within the normal range. PROM1 biallelic cases showed severe functional impairment on ffERG, while most monoallelic cases retained normal responses. In the biallelic cohort, four of four (100%) of patients had severely attenuated or extinguished photopic responses. In the monoallelic PROM1 group, four of five (80%) monoallelic PROM1 patients had normal photopic responses, and P2-2 had mildly attenuated photopic responses. Individuals with biallelic variants exhibited earlier disease onset, more severe retinal degeneration, and significantly reduced retinal function compared with those with monoallelic variants. These observations highlight the role of loss-of-function mechanisms in more aggressive disease courses and underscore the importance of considering zygosity when determining prognosis and planning gene-based therapies. Full article

Pupil cycle time (PCT) estimates the dynamics of a biofeedback loop established between pupil size and stimulus luminance, size or colour. The PCT is useful for probing the functional integrity of the retinopupillary circuits, and is therefore potentially applicable for assessing the effects of damage due to retinopathies or neuropathies. In previous studies, PCT was measured by manually counting the number of pupil oscillations during a fixed period to calculate the PCT. This method is scarce, requires a good expertise and cannot be used to estimate several PCT parameters, such as the oscillation amplitude or variability. We have developed a computerised setup based on eye-tracking that expands the possibilities of characterising PCT along several dimensions: oscillation frequency and regularity, amplitude and variability, which can be used with a large palette of stimuli (different colours, sizes, shapes or locations), and further allows measuring blinking frequency and eye movements. We used this method to characterise the PCT in young control participants as well as in patients with several pathologies, including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), Stargardt disease (SD), and Leber hereditary optic neuropathy (LHON). We found that PCT is very regular and stable in young healthy participants, with little inter-individual variability. In contrast, several PCT features are altered in older healthy participants as well as in ocular diseases, including slower dynamics, irregular oscillations, and reduced oscillation amplitude. The distinction between patients and healthy participants based on the calculation of the area under the curve of the receiver operating characteristics (AUC of ROC) were dependent on the pathologies and stimuli (0.7 < AUC < 1). PCT nevertheless provides relevant complementary information to assess the physiopathology of ocular diseases and to probe the functioning of retino-pupillary circuits. Full article

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterized by progressive photoreceptor degeneration and vision loss. While current management is largely supportive—relying on visual aids, orientation training, and nutritional supplementation—these interventions offer only symptomatic relief and do not halt disease progression. Advances in molecular genetics have led to the development of targeted treatments, including gene replacement therapy, RNA-based therapies, and CRISPR/Cas9 gene editing, offering promising strategies for disease modification. The approval of voretigene neparvovec for RPE65-associated RP marked a milestone in gene therapy, while ongoing trials targeting mutations in RPGR, USH2A, and CEP290 are expanding therapeutic options. Optogenetic therapy and stem cell transplantation represent additional strategies, particularly for patients with advanced disease. Challenges persist in delivery efficiency, immune responses, and treating large or dominant-negative mutations. Non-viral vectors, nanoparticle systems, and artificial intelligence-guided diagnostics are being explored to address these limitations and support personalized care. This review summarizes the current and emerging therapeutic landscape for RP, highlighting the shift toward precision medicine and the need for continued innovation to overcome genetic and phenotypic variability. Full article

Background: Syndromic inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of disorders, involving the retina and additional organs. Over 80 forms of syndromic IRD have been described. Methods: We aimed to phenotypically and genotypically characterize a cohort of 171 individuals from 140 Israeli families with syndromic IRD. Ophthalmic examination included best corrected visual acuity, fundus examination, visual field testing, retinal imaging and electrophysiological evaluation. Most participants were also evaluated by specialists in fields relevant to their extra-retinal symptoms. Genetic analyses included haplotype analysis, homozygosity mapping, Sanger sequencing and next-generation sequencing. Results: In total, 51% of the families in the cohort were consanguineous. The largest ethnic group was Muslim Arabs. The most common phenotype was Usher syndrome (USH). The most common causative gene was USH2A. In 29% of the families, genetic analysis led to a revised or modified clinical diagnosis. This included confirmation of an atypical USH diagnosis for individuals with late-onset retinitis pigmentosa (RP) and/or hearing loss (HL); diagnosis of Heimler syndrome in individuals with biallelic pathogenic variants in PEX6 and an original diagnosis of USH or nonsyndromic RP; and diagnosis of a mild form of Leber congenital amaurosis with early-onset deafness (LCAEOD) in an individual with a heterozygous pathogenic variant in TUBB4B and an original diagnosis of USH. Novel genotype–phenotype correlations included biallelic pathogenic variants in KATNIP, previously associated with Joubert syndrome (JBTS), in an individual who presented with kidney disease and IRD, but no other features of JBTS. Conclusions: Syndromic IRDs are a highly heterogeneous group of disorders. The rarity of some of these syndromes on one hand, and the co-occurrence of several syndromic and nonsyndromic conditions in some individuals, on the other hand, complicates the diagnostic process. Genetic analysis is the ultimate way to obtain an accurate clinical diagnosis in these individuals. Full article

We have previously demonstrated the ability of inhibitors of LSD1 and HDAC1 to block rod degeneration, preserve vision, maintain transcription of rod photoreceptor genes, and downregulate transcripts involved in cell death, gliosis, and inflammation in the mouse model of Retinitis Pigmentosa (RP), rd10. To extend our findings, we tested the hypothesis that this effect was due to altered chromatin structure by using a range of inhibitors of chromatin condensation to prevent photoreceptor degeneration in the rd10 mouse model. We used inhibitors for both G9A/GLP, which catalyzes methylation of H3K9, and EZH2, which catalyzes trimethylation of H3K27, and compared them to the actions of inhibitors of LSD1 and HDAC. All the inhibitors are likely to decondense chromatin and all preserve, to different extents, retinas from degeneration in rd10 mice, but they act through different metabolic pathways. One group of inhibitors, modifiers for LSD1 and EZH2, demonstrate a high level of maintenance of rod-specific transcripts, activation of Ca²⁺ and Wnt signaling pathways with the inhibition of antigen processing and presentation, immune response, and microglia phagocytosis. Another group of inhibitors, modifiers for HDAC and G9A/GLP, work through upregulation of NGF-stimulated transcription, while downregulating genes belong to immune response, extracellular matrix, cholesterol signaling, and programmed cell death. Our results provide robust support for our hypothesis that inhibition of chromatin condensation can be sufficient to prevent rod death in rd10 mice. Full article

Dark adaptometry is a non-invasive functional test that assesses the retina’s ability to recover sensitivity in low-light conditions following photobleaching. This review explores the physiological mechanisms underlying dark adaptation (DA), including photopigment regeneration and the critical role of the retinal pigment epithelium in the visual cycle. We detail clinical protocols for dark adaptometry using modern instruments such as the AdaptDx, highlighting methodological advances that improve testing efficiency and reproducibility. The clinical utility of dark adaptometry is examined across a range of inherited and acquired retinal disorders, including age-related macular degeneration (AMD), retinitis pigmentosa (RP), Stargardt disease, diabetic retinopathy (DR), cone–rod dystrophy (CRD), vitamin A deficiency, and congenital stationary night blindness (CSNB). Dark adaptometry has emerged as a sensitive biomarker capable of detecting functional deficits before structural changes are evident, making it a valuable tool for early diagnosis and monitoring disease progression. However, limitations such as age-related variability, patient compliance, and lack of standardization remain challenges to broader clinical adoption. Continued refinement of dark adaptometry protocols and instrumentation is essential to maximize its diagnostic potential in ophthalmic practice. Full article

Rhodopsin, a G-protein-coupled receptor (GPCR) comprising the protein opsin covalently linked to the chromophore 11-cis retinal, is pivotal in visual phototransduction. Mutations in the gene encoding rhodopsin (RHO) can cause opsin misfolding or reduce its stability, resulting in retinal degenerative disorders such as retinitis pigmentosa (RP). Current therapeutic strategies employing retinoid-based chaperones partially rescue the folding and trafficking of mutant rhodopsin, but are limited by inherent toxicity and instability due to photoinduced isomerization. In the present work, a pharmacophore-based virtual screening protocol combined with molecular docking and molecular dynamics simulations was employed, leading to the identification of a novel non-retinoid opsin ligand that can potentially act as a pharmacological chaperone. Biological validation confirmed that the compound VS1 binds opsin effectively, representing a valuable starting point for structure-based optimization studies aimed at identifying new opsin stabilizers. Full article

Objectives: To evaluate the patient-reported impact of retinitis pigmentosa (RP) in a large patient cohort to identify relevant disease-related disadvantages as key aspects for the improvement of ophthalmic and social care. Methods: Consecutive patients with molecularly confirmed RP older than 18 years of age were identified in two tertiary care centers in Germany. Patients were contacted to participate in an anonymized patient query regarding the impact of RP on their vocational training, professional career, and social, familial, and personal life, as well as their experience with ophthalmologic care. Results: Out of 241 contacted patients, 162 responded (67.2%; 52.5% female, 67.3% younger than 50 years of age). While the impact of RP on vocational training was limited, professional careers were frequently disrupted with early retirement rates of 39.8% (≥40 years of age) to 50% (≥50 years of age). Most respondents felt restricted in their participation in public life (66.3%). One-fifth complained about financial restrictions; however, one-third of this number did not obtain financial help. A negative impact on familial life (21.4%) was less frequently reported compared to personal impairments, especially anxiety (74.5%) and depression (24.2%). Most respondents considered their ophthalmic care as adequate; however, a delayed diagnosis (≥two years: 28.6%) and initial misdiagnosis (24.0%) were frequent. Insufficient psychological support was the major complaint about professional care. Conclusions: RP affects the lives of patients in multiple aspects. Ophthalmic and social care providers should focus on the acceleration of the diagnostic process, as well as easy access to financial assistance and psychological support, as key areas for improvement. Improvements in these areas are expected to reduce challenges for patients. They should have an impact on rehabilitation, participation in public life, and quality of life. Full article

Retinitis Pigmentosa (RP) is a progressive retinal disorder that leads to vision loss and blindness. Accurate staging of RP is crucial for effective treatment planning and disease management. This study aims to develop an objective and reliable method for RP staging by integrating handcrafted features extracted from visual field (VF) grayscale and multifocal electroretinography (mfERG) P1 wave amplitude maps using machine-learning models. Four machine-learning models were evaluated using features derived from VF grayscale maps (GLCM and gray tone features) and mfERG P1 amplitude maps (RGB and HSV features). Additionally, feature selection was performed using the Random Forest (RF) algorithm to identify the most relevant features. The experimental results showed that the Support Vector Machine (SVM) model achieved the highest classification performance with 98.39% accuracy, 98.26% precision, 98.55% recall, 98.41% F1 score, and 99.17% specificity using the seven most important features: RGB Entropy_R, GLCM Contrast_90°, RGB Std_R, GLCM Homogeneity_90°, RGB Energy_R, Histogram Kurtosis, and GLCM Energy_90°. These findings demonstrate that fusing grayscale and amplitude maps provides an effective approach for RP staging. The proposed method may serve as an objective, automated decision-support tool for ophthalmologists, enhancing clinical evaluations and enabling personalized treatment strategies for RP patients. Full article

Stem cell therapy has emerged as a promising approach for treating various retinal diseases, particularly degenerative retinal diseases such as geographic atrophy in age-related macular degeneration (AMD), retinitis pigmentosa (RP), and Stargardt disease. A wide variety of imaging techniques have been employed in both preclinical and clinical settings to assess the efficacy and safety of stem cell therapy for retinal diseases. These techniques can be classified into two categories: methods for imaging stem cells and those for the overall morphology and function of the retina. The techniques employed for stem cell imaging include optical imaging, magnetic resonance imaging (MRI), and radionuclide imaging. Additional imaging techniques include fundus photography, fluorescein angiography, and fundus autofluorescence. Each technique has its own advantages and disadvantages, and thus, the use of multimodal imaging can help to overcome the shortcomings and achieve a more comprehensive evaluation of stem cell therapy in retinal disease. This review discusses the characteristics of the main techniques and cell-labeling techniques applied in stem cell therapy, with a particular focus on the applications of multimodal imaging. Furthermore, this review discusses the challenges and prospects of multimodal imaging in stem cell therapy for retinal disease. Full article

Disease-causing variants in the IDH3A gene are associated with autosomal recessive retinitis pigmentosa 90 (RP90) and Leber congenital amaurosis, with or without macular pseudocoloboma. Here, we report two patients: one compound heterozygous for IDH3A c.364G>A, p.(Ala122Thr), which has conflicting classifications, and for IDH3A c.293C>T, p.(Pro98Leu), which is likely pathogenic, and the other homozygous for IDH3A c.364G>A, p.(Ala122Thr). This study is aimed at providing evidence to link the latter variants to a clinical phenotype. The first patient was a 6-year-old girl, and the second patient was a 29-year-old female. In both patients, the diagnostic assessments were consistent with the phenotype of RP, characterized by macular pseudocoloboma but of varying severity. Patients’ phenotypes suggest that the c.293C>T, p.(Pro98Leu) variant is linked to a more severe and extensive clinical phenotype, while the c.364G>A, p.(Ala122Thr) variant results in a milder condition, primarily limited to retinal involvement. In Patient 2, the presence of both global and local stereopsis, indicating advanced visual development, suggests that the p.(Ala122Thr) missense variant may act as a hypomorphic allele which likely allows for some residual enzymatic activity of the IDH3A protein. This report highlights that macular pseudocoloboma can manifest even in the absence of a null variant. In contrast, more severe symptoms, such as mitochondrial encephalopathy, seem to be associated with the presence of a null allele. Furthermore, to the best of our knowledge, this is the first report of the IDH3A c.293C>T, p.(Pro98Leu) variant. Full article