Search Results (235)

Background/Objectives: Retinitis pigmentosa is a degenerative retinal disease and a major cause of inherited blindness globally. The pro-survival kinase AKT is downregulated in degenerating photoreceptors in retinitis pigmentosa, and its activation has shown neuroprotective effects in retinitis pigmentosa and other neurodegenerative disorders. In this study, we evaluated the therapeutic potential of SC79, a pharmaceutical AKT activator, in two mouse models of retinitis pigmentosa, rd1.GFP and RhoP23H.GFP. Methods: SC79 was administered intravitreally at postnatal day 12 (P12) and analysis was conducted at P16. Results: SC79 at 10 µM was well tolerated in wildtype mice, with no reduction in retinal function or thickness. In rd1.GFP mice, SC79 partially preserved peripheral outer nuclear layer (ONL) thickness, improved rod photoreceptor-driven optomotor contrast sensitivity responses, and improved cone photoreceptor morphology. Immunohistochemistry of retinal sections indicated AKT-related protein expression changes in both sham and SC79-treated rd1.GFP retinas, with sham injections leading to decreases in this pathway and SC79 injections restoring this back to uninjected protein levels or higher, indicating the damage from intravitreal injections can induce AKT-related protein expression changes. In RhoP23H.GFP mice, changes to the visual response from the therapeutic effects of SC79 were not detectable. An increased dosage of SC79 at 100 µM was evaluated in wildtype mice and showed no major toxic effects, although it did not confer neuroprotective benefits in either disease model. Conclusions: These results demonstrate the potential therapeutic effect of AKT pathway modulation for preserving photoreceptors in recessive retinitis pigmentosa, with further optimisation of treatment delivery required. Full article

For retinal degenerative diseases, advanced therapies such as gene therapy and retinal stem cell therapy have emerged as promising treatments, which are often delivered through subretinal injection. However, clinical subretinal injection remains challenging due to the extremely high precision requirements, lack of depth information, and the physiological limitations of manual operation, often leading to complications such as hypotony and globe atrophy. To address these challenges, this study proposes a novel ophthalmic surgical robotic system designed for high-precision subretinal injections. The robotic system incorporate a remote center of motion mechanism for its mechanical structure and employs a master–slave control system to achieve motion scaling. A microscope-integrated optical coherence tomography device is applied to provide real-time microscopic imaging and depth information. The design and performance of the proposed system are validated through simulations and experiments. Precision tests demonstrate that the system achieves an overall positioning accuracy of less than 30 $\mathsf{\mu }$m, with injection positioning accuracy under 20 $\mathsf{\mu }$m. Subretinal injection experiments conducted on artificial eye models further validate the clinical feasibility of the robotic system. Full article

Retinitis pigmentosa (RP), an inherited retinal disorder, leads to progressive photoreceptor degeneration and irreversible blindness, with limited treatment options available. Emerging evidence implicates microRNAs (miRNAs) in the pathogenesis of retinal disease, yet understanding of their specific roles in RP remains incomplete. In this study, we employed high-throughput RNA sequencing to profile miRNA expression in a rd1 RP mouse model at postnatal day 14. Our analysis revealed 40 upregulated and 27 downregulated miRNAs in rd1 retinas compared to controls. Notably, miR-142a-5p, miR-223-3p, and miR-653-5p were significantly elevated, while miR-25-3p was downregulated. Given miR-142a-5p’s established roles in apoptosis and inflammation, we investigated its contribution to retinal degeneration. Knockdown of miR-142a-5p in rd1 mice improved retinal function and preserved outer nuclear layer thickness, suggesting a protective effect against photoreceptor loss. These findings highlight miR-142a-5p as a key regulator of RP progression and a promising therapeutic target for mitigating vision loss in retinal degenerative diseases. Full article

Background/Objectives: To compare changes in the thickness of retinal layers between patients with amyotrophic lateral sclerosis (ALS) and healthy controls using optical coherence tomography. Amyotrophic lateral sclerosis is a degenerative disease of the upper and lower motoneurons with a rapidly progressive course, but non-motor symptoms such as decreased ocular motility and reduced visual acuity have also been reported. Specific biomarkers or surrogate parameters assessing neurodegeneration in ALS are of interest. Methods: In a retrospective, longitudinal study using optic coherence tomography of the retinal layers, we compared changes in the thickness of the layers between patients with ALS and healthy controls. Correlations to clinical scores, such as the modified ranking scale, were analyzed. Results: In our cohort of patients with early ALS (disease duration 5.15 ± 21.4 months at baseline), we neither observed differences in retinal layer thickness at baseline nor did the thickness changes in any retinal layer differ in comparison to healthy controls at baseline. Moreover, we observed no significant thickness changes over the course of the observational period in our patients with ALS. However, a correlation analysis revealed a negative association of the thickness change rates in the complex of ganglion cell and inner plexiform layer and the inner nuclear layer with a higher modified Rankin scale at follow-up. Conclusions: This study adds to the notion that OCT may not be a suitable tool to monitor atrophy and disease progression in ALS. However, further longitudinal studies with longer follow-up times and larger cohorts are warranted. Full article

Background and Objectives: The aim of this study is to employ quantitative proteomics to elucidate the molecular mechanism and signaling pathways modulated by plasma rich in growth factors (PRGF) in a murine model of geographic atrophy (GA)-like retinal degeneration. Materials and Methods: C57BL/6J mice were used as a model GA-like retinal degeneration by a single systemic NaIO₃ administration. Animals were divided into three groups: Control (PBS), Disease (NaIO₃ + PBS), and PRGF-treated (NaIO₃ + PRGF). After 7 days, retinas and retinal pigment epithelium were collected for proteomic analysis. Proteins were extracted, digested using the FASP method, and analyzed by Data-Independent Acquisition (DIA-PASEF) mass spectrometry; data were processed with DIA-NN and statistically analyzed with Perseus. Functional pathway analysis was performed using Ingenuity Pathway Analysis. Results: A total of 6511 proteins were identified. The Disease model showed the expected deregulation of pathways related to oxidative stress, inflammation, and fibrosis. Comparison between the PRGF and Control groups showed that PRGF significantly reduced oxidative and cellular stress proteins/pathways. In the same way, when PRGF and Disease groups were compared, PRGF treatment showed a significant reduction in pathways associated with inflammation, oxidative stress, and cellular stress. PRGF also activated several homeostatic pathways not only related to neuroprotective pathways but also with the lipid deposition (drusen) reduction. All these results suggest that PRGF treatment exerts a protective effect against NaIO₃-induced retinal damage. Conclusions: These findings suggest that PRGF effectively mitigates the degenerative effects of NaIO₃ by activating specific protective and compensatory signaling pathways in the retina. PRGF is indicated as a promising new therapeutic option for ameliorating age-related macular degeneration progression. Full article

Background: Laser Speckle Flowgraphy (LSFG) is a non-invasive imaging technology that quantitatively evaluates retinal and choroidal blood flow by analyzing speckle patterns generated by laser light scattering. This systematic review summarizes the application of LSFG in two major degenerative retinal diseases: age-related macular degeneration (AMD) and diabetic retinopathy (DR). Methods: A comprehensive literature search (2010–2025) was conducted in PubMed, Cochrane Library and EMBASE according to PRISMA guidelines. Twenty-three studies including a total of 974 eyes (191 AMD, 783 DR) were analyzed. Results: In AMD, LSFG detected baseline reductions in choroidal and retinal perfusion in non-exudative disease, often extending beyond atrophic regions. Anti-VEGF injections produced acute reductions in MBR, particularly with brolucizumab, with partial recovery over time; drug-specific differences suggest a potential impact on geographic atrophy progression. In DR, LSFG revealed early microvascular dysfunction even in asymptomatic eyes. Retinal and choroidal MBR and blowout score correlated with HbA1c, DR severity, and inflammatory mediators. Intravitreal anti-VEGF therapy consistently reduced retinal and choroidal MBR and RFV, while conventional panretinal photocoagulation decreased choroidal flow and vascular caliber more robustly than patterned laser, reflecting oxygenation-driven VEGF modulation. Low baseline MBR predicted higher central macular thickness and reduced therapeutic response in diabetic macular edema. Conclusions: LSFG provides reproducible, rapid, and non-invasive quantitative insights into ocular hemodynamics across degenerative retinal diseases. Its integration into multimodal imaging may facilitate early diagnosis, support personalized management, and assist in the prognostic assessment of retinal and choroidal vascular disorders. Full article

Toxins as channel probes, small guanidinium alkaloids, such as tetrodotoxin and saxitoxin, canonical pore occlusion in voltage-gated Na⁺ channels. Cystine-rich peptides from spiders, scorpions, cone snails, and sea anemones, which act as pore blockers or gating modifiers targeting voltage-sensing domains. Recent structural and electrophysiological studies have identified specific binding sites on ion channels, including the S5–S6 pore loops, outer vestibule and turret regions, and S3–S4 “paddle” motifs in NaV, Kv, and CaV channels. These discrete binding epitopes are recognized by different peptide toxins, enabling isoform- and state-specific modulation; for example, μ-conotoxins bind the NaV pore, whereas charybdotoxin and agitoxin target the Kv outer vestibule. Beyond mechanistic insights, peptide toxins inspire translational strategies, including emerging therapies for retinal degenerative diseases. Photopharmacology using chemical photoswitches allows reversible, light-controlled modulation of ion channels in retinal ganglion cells without genetic manipulation or cell transplantation. Although BENAQ was discovered by small-molecule screening rather than toxin-guided design, its ion channel control demonstrates the potential of toxin-based molecular determinants for engineering synthetic compounds. This review thus integrates structural, functional, and translational perspectives, emphasizing the versatility of animal-derived peptide toxins as molecular probes and as blueprints for precision ion channel modulation in health and disease. Full article

Non-syndromic Inherited Retinal Dystrophies (IRDs) are a set of degenerative retinal diseases that vary clinically and genetically, including Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). IRDs are a significant cause of vision loss in young adults globally. To date, more than 280 genes have been associated with IRD pathogenesis. This study aims to investigate the genetic basis of non-syndromic IRD in the Qatari population and to assess the diagnostic yield of various genetic tests through a retrospective cohort study. Our study identified 49 eligible patients with IRD, 61.2% of whom were Qatari. Rod-dominated phenotypes accounted for 51% of the hereditary retinal diseases in this cohort. Whole-exome sequencing with mitochondrial genome testing (WES Plus) was the most frequently utilized genetic test. A total of 55 variants were identified across 32 IRD-associated genes. Of the 49 cases, 34 (69.4%) were initially classified as solved, and an additional five were likely to be solved based on familial segregation analysis. Variants in the ABCA4 gene were the most commonly observed, present in eight patients, with the c.5882G>A variant being the most recurrent, identified in three of these cases. Specific genes exhibited recurrent variations, including pan-ethnic variants that are common across multiple populations. These variants merit prioritization in testing due to their global prevalence. WES is recommended as a first-tier test for non-syndromic IRD cases, as it accelerates diagnosis, facilitates earlier interventions, and provides a comprehensive genetic picture by incorporating information from family members. Moreover, our study highlighted the significance of performing family segregation analyses in identifying possible causative variants. This is the first genetic study of IRD in Qatar, laying the groundwork for further research on the epidemiology and genetics of non-syndromic IRD in this understudied region. Full article

Retinal degeneration (RD) is an intractable ophthalmic disorder with no effective treatments, and its pathogenesis is complex, involving multiple genes. Endoplasmic reticulum (ER) stress and neuronal apoptosis are key factors that drive neurodegeneration in retinal degeneration. B cell receptor-associated protein 31 (BAP31) is a transmembrane protein predominantly found in the ER, which plays an important role in regulating ER stress and apoptosis. To date, no studies have directly confirmed the association between BAP31 and retinal degenerative diseases. However, considering that ER dysfunction is a key trigger for retinal photoreceptor cell damage and that BAP31 acts as a core regulator of ER function, we hypothesize that BAP31 may be involved in the development of retinal degeneration by regulating ER homeostasis. Our study aimed to investigate the pathogenic mechanisms of BAP31 in retinal disorders. A rod-specific conditional knockdown of BAP31 mouse model (Rho-iCre-BAP31^fl/fl(−/−)) was employed to explore the role of BAP31 in retinal pathogenesis. The Rho-iCre-BAP31^fl/fl(−/−) mice exhibited phenotypes similar to retinitis pigmentosa (RP), including decreased ERG responses, photoreceptor degeneration, and reduced visual function. Optical coherence tomography (OCT) results showed that the outer nuclear layer (ONL) of the retina in conditional knockdown mice exhibited progressive thinning after 9 months of age; histopathological examination results were consistent with those of OCT. These findings indicated that the rod photoreceptor cells in the conditional knockdown mice showed damage and irregular arrangement starting at 9 months of age, with more prominent changes by 12 months. RNA sequence analysis of 12-month-old mice indicated enrichment of the phototransduction pathway, with significant downregulation of key genes (rhodopsin, recoverin, Gnat1, Pde6a, and Pde6b) involved in retinal development and phototransduction, along with a marked increase in Gfap expression (indicating glial activation and retinal damage). Quantitative real-time PCR and Western blot analyses showed significant upregulation of unfolded protein response (UPR) marker proteins (BIP, CHOP, XBP1, ATF4, ATF6), demonstrating robust ER stress activation. The findings suggest that BAP31 deficiency induces retinal degeneration, and the activation of the ER stress may contribute to the pathogenic mechanisms underlying this process. Full article

The translocator protein (TSPO), an evolutionarily conserved protein located on the outer mitochondrial membrane, is typically expressed at low levels in the central nervous system under normal physiological conditions. However, its expression can increase in response to various pathological conditions, such as neurodegenerative diseases and neuroinflammation. Retinitis pigmentosa (RP) refers to a group of inherited degenerative diseases of the retina; the progression of the pathology is linked to a chronic inflammatory state that leads to the progressive loss of photoreceptors and ultimately to blindness. One of the key processes contributing to the gradual loss of photoreceptors is neuroinflammation, a mechanism in which the TSPO plays a newly studied role. In this context, TSPO could be an excellent target. In the current study, rd10 mice of both sexes were treated with a TSPO ligand, PIGA1138, as an ophthalmic suspension (1 mg/mL) from post-natal day (P)18 to P30, P60, and P90. Retinal function was evaluated through electroretinography, while visual acuity was assessed using the Prusky Water Maze task. Additionally, molecular analyses were performed to assess TSPO expression, alongside examinations of retinal morphology. Results showed significant retinal preservation, reduced photoreceptor loss, and improved retinal responses, suggesting preserved visual function. These findings highlight PIGA1138’s potential in mitigating retinal degeneration and preserving function in retinal diseases like RP. Full article

Age-related macular degeneration (AMD) is a retinal degenerative disease caused by oxidative stress. Thus, we aimed to reduce oxidative stress through the use of placenta-derived mesenchymal stem cells (PD-MSCs). To induce oxidative stress in ARPE-19 cells, we treated them with 200 µM hydrogen peroxide (H₂O₂) for 2 h and then cocultured them with PD-MSCs. The dissociation of the KEAP1/Nrf2 complex, along with the expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), increased in the coculture group compared with the H₂O₂ treatment group (* p < 0.05). The expression levels of antioxidant genes increased in the cocultured group compared with those in the H₂O₂ treatment group (* p < 0.05), whereas the ROS levels decreased in the cocultured group (* p < 0.05). Additionally, both the expression of mitochondrial dynamics markers and the mitochondrial membrane potential increased when the cells were cocultured with PD-MSCs (* p < 0.05). PD-MSC cocultivation decreased the expression levels of lipoproteins (* p < 0.05). Finally, we confirmed that PD-MSCs promoted the expression of RPE-specific genes in H₂O₂-injured ARPE-19 cells (* p < 0.05). These findings suggest a new aspect of stem cell treatment for AMD induced by oxidative stress. Full article

Optogenetics is a field that emerged with the goal of studying the physiology of nerve cells by selectively expressing opsins—channel proteins that can be activated by light exposure. Once the methodology was established, several research groups sought to express these proteins in damaged nerve tissue to restore proper signal transmission. Over the years, numerous efforts have been made to restore vision in patients with chronic degenerative diseases, particularly retinitis pigmentosa, with clinical trials yielding encouraging results. However, significant challenges remain, such as the difficulty of delivering the signal to specific retinal cells and the complexity of replicating the physiological activation of the target cells. As research continues, optogenetics remains a promising yet evolving field. This review aims to highlight the therapeutic advantages of optogenetics over currently available strategies and to promote further scientific exploration of this emerging discipline. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly, characterized by progressive degeneration of the retinal pigment epithelium (RPE) and photoreceptors in the macula. Current treatment options primarily focus on slowing disease progression in neovascular AMD, while effective therapies for dry AMD remain limited. Optogenetics, a revolutionary technique utilizing light-sensitive proteins (opsins) to control the activity of genetically targeted cells, has emerged as a promising therapeutic strategy for restoring vision in retinal degenerative diseases. In retinal disease models, adeno-associated viruses (AAVs) serve as delivery vectors via intravitreal or subretinal injections. This review explores the principles of optogenetics, its application in preclinical AMD models, and the potential for clinical translation of this approach. We discuss the various optogenetic tools, delivery methods, and the challenges and future directions in harnessing this technology to combat AMD-related vision loss. Full article

Transcorneal electrical stimulation (TES) is a promising treatment for several retinal degenerative diseases (RDDs). TES involves the application of a controlled electrical current to the anterior surface of the cornea, aimed at activating the retina and posterior ocular structures. Dawson–Trick–Litzkow (DTL) and ERG-JET electrodes are among the most widely used for TES. However, their continuous metallic surface design limits spatial resolution and the ability to perform selective ES. In this work, we present the development of a transcorneal electrical stimulation (TES) electrode that, unlike conventional electrodes, enables spatially selective TES. The proposed electrode design consists of an array of 20 independent microelectrodes distributed across the central and paracentral regions of the cornea. The fabrication process combines surface micromachining and flexible electronics technologies, employing only three structural materials: aluminum (Al), titanium (Ti), and polyimide (PI). This material selection is critical for achieving a simplified, reproducible, and low-cost fabrication process. The fabricated electrode was validated through electrical and electrochemical testing. The results show a relatively high electrical conductivity of Al/Ti structures, low electrochemical impedance values—ranging from 791 kΩ to 1.75 MΩ for the clinically relevant frequency range (11 to 30 Hz)—and a high charge storage capacity of 1437 mC/cm². The electrode capacity for electrical signal transmission was demonstrated through in vitro testing. Finally, the applicability of the TES electrode for electroretinogram (ERG) recording was evaluated by measuring its optical transmittance across the visible wavelength range. Full article

Replacement of the retinal pigment epithelium (RPE) is emerging as a promising approach to treat degenerative retinal diseases, including age-related macular degeneration and Stargardt disease, in which RPE function cannot otherwise be restored. Despite the limitations of existing treatments, advances in cell sourcing and surgical methods have enabled initial human trials of RPE transplantation, with early results indicating potential efficacy. This review comprehensively examines the evolution of RPE transplantation in recent decades, highlighting the advantages and limitations of different cell sources and delivery methods. Current clinical trial data are analyzed with a particular focus on immune rejection risks, surgical complications, and long-term safety. Despite encouraging safety profiles, achieving consistent and sustained visual improvement remains a challenge, as vision outcomes might be influenced by factors such as disease stage at intervention, transplantation site, number of cells transplanted, and duration of follow-up. Key challenges, such as cell or graft survival and integration with the host retina, are discussed in depth, as overcoming these obstacles is essential for achieving stable and effective RPE replacement. Future research directions, including innovations in biomaterials, molecular modification strategies, and personalized approaches, hold promise for enhancing the efficacy and durability of RPE transplantation for retinal disease. Full article