Retinal Cells Research Articles

A Serum Resistant Polymer with Exceptional Endosomal Escape and mRNA Delivery Efficacy for CRISPR Gene Therapy.

Nanoparticle-based mRNA delivery offers a versatile platform for innovative therapies. However, most of the current delivery systems are limited by poor serum tolerance, suboptimal endosomal escape and mRNA delivery efficacy. Herein, a highly efficient mRNA-delivering material is identified from a library of fluoropolymers. The lead material FD17 shows exceptional serum stability and endosomal escape, enabling efficient mRNA delivery into various cell types, surpassing commercial mRNA delivery reagents such as Lipofectamine 3000. The formed mRNA nanoparticles adsorb abundant serum albumin on the surface, which facilitates cellular uptake via scavenger receptor-mediated endocytosis. FD17 enables the delivery of mRNAs encoding CRE, Cas9, and base editor hyCBE for efficient genome editing. The material mediates CRISPR/Cas9 gene therapy via intraocular injection effectively down-regulates vascular endothelial growth factor A in retinal pigment epithelial cells of mice, yielding promising therapeutic responses against laser-induced choroidal neovascularization. The discovered material in this study shows great promise for the development of mRNA therapeutics to combat a wide range of diseases.

A single-nucleus RNA sequencing atlas of the postnatal retina of the shark Scyliorhinus canicula

The retina, whose basic cellular structure is highly conserved across vertebrates, constitutes an accessible system for studying the central nervous system. In recent years, single-cell RNA sequencing studies have uncovered cellular diversity in the retina of a variety of species, providing new insights on retinal evolution and development. However, similar data in cartilaginous fishes, the sister group to all other extant jawed vertebrates, are still lacking. Here, we present a single-nucleus RNA sequencing atlas of the postnatal retina of the catshark Scyliorhinus canicula, consisting of the expression profiles for 17,438 individual cells from three female, juvenile catshark specimens. Unsupervised clustering revealed 22 distinct cell types comprising all major retinal cell classes, as well as retinal progenitor cells (whose presence reflects the persistence of proliferative activity in postnatal stages in sharks) and oligodendrocytes. Thus, our dataset serves as a foundation for further studies on the development and function of the catshark retina. Moreover, integration of our atlas with data from other species will allow for a better understanding of vertebrate retinal evolution.

Geographic Atrophy in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD), a condition of multifactorial origin, is a major cause of irreversible vision loss in industrialized countries. The dry late stage of the disease, known as geographic atrophy (GA), is characterized by progressive loss of photoreceptor cells and retinal pigment epithelial cells in the central retina. An estimated 300 000 to 550 000 people in Germany suffer from GA. This review is based on pertinent literature retrieved by a selective search in the PubMed and Web of Science databases. In 2023, the complement inhibitors pegcetacoplan and avacincaptad pegol were approved in the USA for repeated intravitreal injections and thereby became the first drugs ever approved for the treatment of GA. In Europe, the marketing authorization application for both drugs was withdrawn by the manufacturers after a negative judgment was expressed by the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use. The EMA stated that the significant slowing of atrophy progression that had been achieved in the approval trials did not lead to any clinically relevant functional benefit for the patients. Further treatment approaches, including gene therapy, are now being studied in clinical trials. There is evidence that micronutrients may slow the progression of atrophy. In Europe at present, there is no approved treatment for GA due to AMD. There is thus a continuing need for preventive and rehabilitative measures such as smoking cessation, a balanced diet, and magnifying visual aids for patients in the advanced stages of the disease.

Ibudilast Protects Retinal Bipolar Cells From Excitotoxic Retinal Damage and Activates the mTOR Pathway.

Ibudilast, an inhibitor of macrophage migration inhibitory factor (MIF) and phosphodiesterase (PDE), has been recently shown to have neuroprotective effects in a variety of neurologic diseases. We utilize a chick excitotoxic retinal damage model to investigate ibudilast's potential to protect retinal neurons. Using single cell RNA-sequencing (scRNA-seq), we find that MIF, putative MIF receptors CD74 and CD44, and several PDEs are upregulated in different retinal cells during damage. Intravitreal ibudilast is well tolerated in the eye and causes no evidence of toxicity. Ibudilast effectively protects neurons in the inner nuclear layer from NMDA-induced cell death, restores retinal layer thickness on spectral domain optical coherence tomography (SD-OCT), and preserves retinal neuron function, particularly for the ON bipolar cells, as assessed by electroretinography. PDE inhibition seems essential for ibudilast's neuroprotection, as AV1013, the analogue that lacks PDE inhibitor activity, is ineffective. scRNA-seq analysis reveals upregulation of multiple signaling pathways, including mTOR, in damaged Müller glia (MG) with ibudilast treatment compared to AV1013. Components of mTORC1 and mTORC2 are upregulated in both bipolar cells and MG with ibudilast. The mTOR inhibitor rapamycin blocked accumulation of pS6 but did not reduce TUNEL positive dying cells. Additionally, through ligand-receptor interaction analysis, crosstalk between bipolar cells and MG may be important for neuroprotection. We have identified several paracrine signaling pathways that are known to contribute to cell survival and neuroprotection and might play essential roles in ibudilast function. These findings highlight ibudilast's potential to protect inner retinal neurons during damage and show promise for future clinical translation.

Expression of Osteopontin in M2 and M4 Intrinsically Photosensitive Retinal Ganglion Cells in the Mouse Retina

Expression of Osteopontin in M2 and M4 Intrinsically Photosensitive Retinal Ganglion Cells in the Mouse Retina

Loss of 18q Alters TGFβ Signalling Affecting Anteroposterior Neuroectodermal Fate in Human Embryonic Stem Cells.

Chromosomal abnormalities acquired during cell culture can compromise the differentiation potential of human pluripotent stem cells (hPSCs). In this work, we identified a diminished differentiation capacity to retinal progenitor cells in human embryonic stem cells (hESCs) with complex karyotypes that had in common the loss of part of chromosome 18q. Time-course gene-expression analysis during spontaneous differentiation and single-cell RNA sequencing found that these variant cell lines poorly specified into anterior neuroectoderm, and, when progressing through differentiation, they yielded poorly pigmented cells, with proliferating and pluripotent cell populations. The variant cell lines showed dysregulation of TGFβ signalling during differentiation, and chemical modulation of the TGFβ pathways showed that the basis of the improper specification was due to imbalances in the anteroposterior neuroectodermal fate commitment.

ERG responses to high-frequency flickers require FAT3 signaling in mouse retinal bipolar cells.

Vision is initiated by the reception of light by photoreceptors and subsequent processing via downstream retinal neurons. Proper circuit organization depends on the multifunctional tissue polarity protein FAT3, which is required for amacrine cell connectivity and retinal lamination. Here, we investigated the retinal function of Fat3 mutant mice and found decreases in both electroretinography and perceptual responses to high-frequency flashes. These defects did not correlate with abnormal amacrine cell wiring, pointing instead to a role in bipolar cell subtypes that also express FAT3. The role of FAT3 in the response to high temporal frequency flashes depends upon its ability to transduce an intracellular signal. Mechanistically, FAT3 binds to the synaptic protein PTPσ intracellularly and is required to localize GRIK1 to OFF-cone bipolar cell synapses with cone photoreceptors. These findings expand the repertoire of FAT3's functions and reveal its importance in bipolar cells for high-frequency light response.

Evidence for a Functional Link Between the Nrf2 Signalling Pathway and Cytoprotective Effect of S-Petasin in Human Retinal Pigment Epithelium Cells Exposed to Oxidative Stress

The retinal pigment epithelium (RPE) is a highly specialised monolayer epithelium subjected to constant oxidative stress, which, in the long term, favours the development of a complex pathological process that is the underlying cause of macular damage. Therefore, counteracting the overproduction of ROS is the best-researched approach to preserve the functional integrity of the RPE. S-Petasin, a secondary metabolite extracted from the plant Petasites hybridus, has numerous biological effects, which highlight its anti-inflammatory and antioxidative properties. The aim of our study is to investigate whether S-Petasin exerts cytoprotective effects by protecting the RPE from oxidative damage. The effects of pretreatment with S-Petasin were assessed by the determination of the cell viability, intracellular ROS levels, activation of the Nrf2 pathway and the resulting post-transcriptional antioxidant/antiapoptotic response. Our results show that S-Petasin pretreatment (1) reduces intracellular ROS levels, improving cell viability of RPE exposed to oxidative damage; (2) activates the Nrf2 signalling pathway, modulating the post-transcriptional response of its antioxidant chemical biomarkers; (3) reduces the Bax levels, and an increase in those of Bcl-2, with a concomitant downregulation of the Bax/Bc-2 ratio. Overall, our results provide the first evidence that S-Petasin is able to protect the RPE from oxidative damage

The effect of molecular chaperone mediated autophagy on ApoE expression in retinal pigment epithelial cells: Molecular structure and protein action mechanism.

Chaperone mediated autophagy (CMA) represents a specialized mechanism of lysosomal protein breakdown, playing a crucial role as a metabolic pathway that helps to regulate and sustain cellular and systemic physiological equilibrium. Within the CMA process, proteins that contain sequences similar to KFERQ are specifically identified by the heat shock cognate protein 70. These proteins are then chaperoned to the lysosomes for subsequent degradation, a process facilitated by the lysosome associated membrane protein 2A. This particular research employed bioinformatics techniques to systematically screen for potential substrates of CMA. ApoE has a KFERQ like motif, which may be a substrate for CMA. Under conditions of starvation, hypoxia, H2O2, PA, and NaIO3, the expression of the rate limiting factor LAMP2A in CMA and ApoE increased significantly (P<0.05). Under conditions of NaIO3, the expression of CMA related gene mRNA increased significantly (P<0.05). When we use lysosomal blocker CQ to inhibit CMA activity, the expression level of ApoE in retinal pigment epithelial cells increased, and the difference was statistically significant (P<0.05). When we inhibit CMA, the accumulation of ApoE in retinal pigment epithelial cells increases and cell viability decreases. When we activate CMA, the accumulation of ApoE decreases and cell viability increases. In retinal pigment epithelial cells, the drusen associated protein ApoE can be degraded through the CMA pathway.

Differentiation of primary retinal progenitor cells into retinal ganglion-like cells using low dose cytarabine.

The death of retinal ganglion cells (RGCs) is a key factor in the pathophysiology of all forms of glaucoma. RGC culture serves as a simple system for establishing and testing candidate therapies. This study aimed to explore the differentiation of primary retinal progenitor cells (RPCs) into RGC-like cells induced by low-dose cytarabine (Ara-C). RPCs were isolated from the retina of newborn rats and cultured in vitro. Different concentrations of Ara-C were added to the culture medium to induce the differentiation of RPCs into RGC-like cells. Differentiation efficiency was assessed through immunofluorescence staining and cell counting. The addition of Ara-C significantly increased the number of Brn3a/RBPMS double-positive cells. The RPC-RGCs induced displayed characteristic features of RGCs, with roughly 80.9%±6.2% of the cells positive for both TuJ1/NeuN and 77.5%±4.9% for Brn3a/RBPMS. The study demonstrates that the addition of Ara-C to primary cultures of rat RPCs can enhance their differentiation into RGC-like cells, providing a simple and rapid method for obtaining RGC-like cells with a relatively high purity. This method shows considerable promise for advancing glaucoma research and potential therapeutic strategies to restore vision after RGC loss.

Baicalein Modulates Endoplasmic Reticulum Stress by Activating SIRT3 to Attenuate the Dysfunction of Retinal Microvascular Endothelial Cells under High Glucose Conditions.

High glucose-induced alterations in the retinal microvasculature are major contributors to vision loss and deterioration. Baicalein, known for its protective effect on blood vessels and endothelial cells, is a potential therapeutic agent for diabetes-induced retinal dysfunction. This study aims to investigate the impact and mechanism of baicalein on high glucose-induced dysfunction in retinal microvascular endothelial cells (RMECs). Human RMECs (hRMECs) were exposed to a high glucose condition (30 mM). The effect of various concentrations of baicalein on cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Baicalein's effects on sirtuin 3 (SIRT3) expression in hRMECs were evaluated via western blot and quantitative real-time polymerase chain reaction. Additionally, the regulatory role of baicalein was examined by knocking down SIRT3. Cell permeability and migration were assessed using the Transwell assay, and tube formation was evaluated by tube formation assay. Moreover, western blot analysis was employed to investigate protein expression related to endoplasmic reticulum stress (ERS). Baicalein markedly inhibited the increase in the viability, permeability, tube formation and migration of hRMECs induced by high glucose. Moreover, it significantly reduced the intracellular ERS levels in high glucose-induced hRMECs. Notably, SIRT3 knockdown reversed the inhibition of baicalein on hRMECs. In summary, baicalein mitigates high glucose-mediated ERS by up-regulating SIRT3 expression, thereby maintaining the normal function of RMECs.

MiRNAs, piRNAs, and lncRNAs: A triad of non-coding RNAs regulating the neurovascular unit in diabetic retinopathy and their therapeutic potentials.

Diabetic Retinopathy (DR), a leading complication of diabetes mellitus, has long been considered as a microvascular disease of the retina. However, recent evidence suggests that DR is a neurovascular disease, characterized by the degeneration of retinal neural tissue and microvascular abnormalities encompassing ischemia, neovascularization, and blood-retinal barrier breakdown, ultimately leading to blindness. The intricate relationship between the retina and vascular cells constitutes a neurovascular unit, a multi-cellular framework of retinal neurons, glial cells, immune cells, and vascular cells, which facilitates neurovascular coupling, linking neuronal activity to blood flow. These interconnections between the neurovascular components get compromised due to hyperglycemia and are further associated with the progression of DR early on in the disease. As a result, therapeutic approaches are needed to avert the advancement of DR by acting at its initial stage to delay or prevent the pathogenesis. Non-coding RNAs (ncRNAs) such as microRNAs, piwi-interacting RNAs, and long non-coding RNAs regulate various cellular components in the neurovascular unit. These ncRNAs are key regulators of neurodegeneration, apoptosis, inflammation, and oxidative stress in DR. In this review, research related to alterations in the expression of ncRNAs and, correspondingly, their effect on the disintegration of the neurovascular coupling will be discussed briefly to understand the potential of ncRNAs as therapeutic targets for treating this debilitating disease.

Epigallocatechin gallate ameliorates retinal pigment epithelial cell damage via the CYFIP2 /AKT pathway.

Age-related macular degeneration (AMD) is a representative age-related ophthalmic disease, and the pathogenesis of AMD remains unclear. This research intended to determine whether epigallocatechin gallate (EGCG) could alleviate the progression of AMD and the possible mechanism. We constructed three groups of mice (young, aged, and EGCG), and HE and TUNEL staining of retinal tissues was performed to observe the structural changes in the retinal pigment epithelial (RPE) layer and the level of apoptosis, respectively. Through RNA-Sequencing analysis of retinal tissues and by RT-qPCR, GO, KEGG, and literature analyses, we identified cytoplasmic fragile X mental retardation 1-interacting protein 2 (CYFIP2) as a possible effector gene for EGCG action and validated its role by immunofluorescent and western blotting experiments. The CCK-8 and Hoechst 33342 apoptosis assays, and western blotting and qRT-PCR assays showed that EGCG reduced hydrogen peroxide (H2O2)-induced apoptosis in adult human RPE (ARPE-19) cells, and the expression of Cyfip2 was changed accordingly. RNA interference analysis indicated that Cyfip2 knockdown alleviated H2O2-induced ARPE apoptosis, while its overexpression weakened EGCG's protective effect. Western blot analysis showed that Cyfip2 mediated the anti-apoptotic effect of EGCG by modulating the level of protein kinase B (Akt) phosphorylation in ARPE cells, and the activation level of phosphorylated AKT (p-AKT Ser473) in retinal tissue of the EGCG-fed group was higher than that of the aged group. Taken together, this study suggests that EGCG plays a protective role in the development of AMD and the apoptosis of ARPE cells through the Cyfip2/AKT pathway.

Proteome of Pericytes from Retinal Vasculature of Diabetic Donor Eyes

Retinal pericytes (PCs) are contractile microvascular smooth muscle cells that wrap around the endothelial cells (ECs) maintaining intact retinal vasculature (RV) with a 1:1 ratio. Microvascular complications like Diabetic Retinopathy (DR) due to chronic Diabetes causes apoptotic loss of PCs followed by diminished vessel stability, EC apoptosis, and ischemia, leading to retinal angiogenesis, and eventually severe vision loss. This study aimed to analyze the proteins in PCs isolated from the RV of diabetic human donor eyes and compare them with remaining mixed population (MP) of retinal vascular cells. PCs and MP proteomes were analyzed using semi-quantitative proteomics. Proteins were extracted, quantified, and analyzed in duplicate using LC-MS/MS on a Tandem mass spectrometer. Overall, 42 PC and 27 MP proteins, with 19 shared proteins, were identified. Functional enrichment analysis indicated that PC proteins share common biological processes, such as negative regulation of fibrinolysis and vLDL particle remodeling, nitric oxide transport, phospholipid efflux, positive control over the clearance of apoptotic cells, chondrocyte proliferation, lipoprotein lipase activity, and oxidative stress-induced intrinsic atrophic signaling pathways. In the fold enrichment analysis, the PC proteins were associated with cholesterol metabolism, Complement and coagulant, ECM-receptor interaction, longevity regulating pathway, Peroxisome proliferator-activated receptors (PPAR), focal adhesion and PI3 Akt signaling pathways. Among the PC proteins, vitronectin, gelsolin, hornerin, apolipoprotein A1, C3, H, and complement Factors C3, C4, and C9 were identified as the most highly ranked proteins in diabetes. The identified unique proteins of retinal PC could prove beneficial as a therapeutic target in the management of DR.

Fractionation and identification of ocular protective compounds from kochiae fructus against oxidative damage in retinal pigment epithelium cells.

Kochiae Fructus, the ripe fruit of Kochia scoparia, is a traditional Chinese medicine commonly used to treat eye discomforts and vision problems. Although Kochiae Fructus is mentioned in many classical Chinese medical texts, its protective effects and the roles of its active phytochemicals in eye treatment still lack scientific exploration. This study aimed to clarify the protective effects and identify the active fractions and compounds of Kochiae Fructus against oxidative stress-induced retinal pigment epithelium (RPE) cell death. Liquid-liquid partitioning was employed to prepare active fractions. Silica gel, RP-18, and Sephadex™ LH-20 gels were used as stationary phases to purify the compounds through column chromatography. Cell models were established by treating ARPE-19 (RPE cell line) with hydrogen peroxide (H₂O₂) and tert-butyl hydroperoxide (TBHP), respectively. The methanol aqueous fraction from ethyl acetate-soluble extract (KSEM) alleviated oxidant-induced RPE cell death in a dose-dependent manner and activated the Nrf2/HO-1 pathway, a critical defense mechanism against oxidative damage. The isolated flavonols in fraction KSEM, hyperoside, quercetin, and kaempferol, reduced oxidant-induced cell mortality, with quercetin showing the strongest effect. Moreover, combination treatment revealed that hyperoside and kaempferol synergistically enhanced the protective effects of quercetin, making the combined treatment more efficient than quercetin alone. The protective effects of Kochiae Fructus against oxidative damage in RPE cell was validated with the KSEM fraction. The compound quercetin was identified as the important contributor. However, the synergistic effect of the hyperoside, quercetin, and kaempferol mixture may play a dominant role in the protective action of Kochiae Fructus. Overall, these findings highlight the potential of Kochiae Fructus and its flavonol mixture as a basis for developing treatments targeting ocular diseases associated with oxidative damage in retina.

Recombinant adeno-associated virus with anti-tumor necrosis factor-alpha in an experimental autoimmune uveitis model.

Uveitis treatment is associated with side effects and inconsistent outcomes. Existing treatments often fail to provide targeted and sustained relief; thus, novel therapeutic approaches are needed. Among these, gene therapy using adeno-associated virus (AAV) vectors target specific retinal cells, show low immunogenicity, and demonstrate sustained gene expression, making it a potential advancement in uveitis treatment. Therefore, we utilized a AAV2 system encapsulating encoded anti-tumor necrosis factor-alpha (TNF-α) antibody to assess its efficacy in the treatment of experimental autoimmune uveitis (EAU) in mice. Compared with the AAV2-GFP group, AAV2-ADA-injected mice showed significantly reduced clinical, OCT, and histopathological scores in EAU with lower percentages of Th1 and Th17 cells in the eyes and higher percentages of Treg cells in the draining lymph nodes (LN). This study demonstrated the safety and effects of AAV2-ADA in EAU treatment, providing a promising therapeutic strategy for uveitis.

Cysteinyl leukotriene receptor 1 modulates retinal immune cells, vascularity and proteolytic activity in aged mice.

Cysteinyl leukotrienes (CysLTs) modulate the immune response, the microvasculature, cell stress and the endosomal-lysosomal system, and are involved in cellular aging. Interestingly, CysLT receptor 1 (Cysltr1) is highly expressed in the retina, a tissue that is strongly affected by the aging process. Thus, we performed an introductory examination to determine a potential importance of Cysltr1 for cells in the neurovascular unit using qPCR and immunofluorescence analysis, and on proteolytic activity in the retinas of aged mice. Aged mice (~84 weeks) were treated orally with vehicle or 10 mg/kg montelukast (MTK), a specific Cysltr1 inhibitor, for 8 weeks, 5x/week. The retinas of young mice (~11 weeks) served as controls. Compared with young control mice, aged mice exhibited increased numbers of microglia and a reduced retinal capillary diameter, but these age-dependent changes were abrogated by MTK treatment. Retinal protein levels of the ubiquitin binding protein sequestosome-1 were amplified by aging, but were reduced by MTK treatment. Interestingly, retinal proteasome activity was decreased in aged mice, whereas Cysltr1 inhibition increased this activity. The reduction in immune cells caused by Cysltr1 suppression may dampen neuroinflammation, a known promoter of tissue aging. Additionally, an increase in capillary diameter after Cysltr1 inhibition could have a beneficial effect on blood flow in aged individuals. Furthermore, the increase in proteolytic activity upon Cysltr1 inhibition could prevent the accumulation of toxic deposits, which is a hallmark of aged tissue. Overall, Cysltr1 is a promising target for modulating the impact of aging on retinal tissue.

Hyperhomocysteinemia-induced VCID results in visual deficits, reduced neuroinflammation and vascular alterations in the retina.

Over recent years, the retina has been increasingly investigated as a potential biomarker for dementia. A number of studies have looked at the effect of Alzheimer's disease (AD) pathology on the retina and the associations of AD with visual deficits. However, while OCT-A has been explored as a biomarker of cerebral small vessel disease (cSVD), studies identifying the specific retinal changes and mechanisms associated with cSVD are lacking. Using our model of hyperhomocysteinemia-induced cSVD, we aimed to identify the effects of cSVD on visual sensitivity and cognition, retinal glial and vascular cells, and neuroinflammatory and cardiovascular gene expression changes. We placed C57Bl6/SJL mice on a HHcy-inducing diet, a model that has been well characterized to have vascular pathologies in the brain similar to pathologic cSVD. After 14 weeks on diet, mice underwent the Visual-Stimuli 4-arm Maze to identify visual deficits. Whole mount retinas were stained for vessels, microglia and astrocytes to identify glial and vascular changes. Finally, neuroinflammatory and cardiovascular gene expression was measured using NanoString's nCounter system. Ultimately, HHcy led to visual changes that specifically affected the reaction to blue and white light, slightly decreased vascular volume and significantly decreased interaction of microglia with the vasculature, as well as downregulation of inflammatory and vascular genes. These changes provide novel insights and reproduce some prior observations. These studies highlight retinal changes in association with cSVD and serve as a precaution when interpreting vision-dependent cognitive testing of cSVD models.

Report of a Rare Syndromic Retinal Dystrophy: Asphyxiating Thoracic Dystrophy (Jeune Syndrome).

Jeune syndrome (JS), first described by Jeune as asphyxiating thoracic dystrophy, is an autosomal recessive osteochondrodysplasia with characteristic skeletal abnormalities and variable renal, hepatic, pancreatic, and ocular complications. Approximately 1 in every 100,000 to 130,000 babies is born with JS. Most patients with JS have respiratory distress due to inadequate lung development and many lose their lives due to respiratory failure. Those who survive have serious comorbidities. In terms of ophthalmological diseases, JS is classified among the hereditary syndromic retinopathies. Most, if not all, hereditary syndromic retinopathies can be analyzed in two main groups: inherited metabolic diseases and ciliopathies. The main cause of ocular pathologies in JS is genetic mutations in ciliary proteins that prevent normal function of retinal photoreceptor cells. Here we describe a patient with JS who presented with the complaint of night blindness. Although Snellen visual acuity was 20/20, the patient's visual function was severely impaired due to photoreceptor dysfunction caused by ciliopathy secondary to the genetic mutation. This case shows that in patients with syndromic comorbidities accompanying nyctalopia, even those with perfect visual acuity, hereditary retinal dystrophies should be considered and asphyxiating thoracic dystrophy (JS) included in the differential diagnosis. Multimodal retinal imaging, including structural and functional assessments, should be used for the diagnosis and genetic counselling should also be provided.

BMP4-GPX4 can improve the ferroptosis phenotype of retinal ganglion cells and enhance their differentiation ability after retinal stem cell transplantation in glaucoma with high intraocular pressure.

Activation of bone morphogenetic protein (BMP) 4 signaling promotes the survival of retinal ganglion cell (RGC) after acute injury. In this study, we investigated the role of the BMP4 signaling pathway in regulating the degeneration of retinal ganglion cells (RGCs) in a mouse glaucoma model and its potential application in retinal stem cell. Our results demonstrate that BMP4-GPX4 not only reduces oxidative stress and iron accumulation but also promotes neuroprotective factors that support the survival of transplanted RSCs into the host retina. These findings suggest a novel therapeutic approach for glaucoma involving the modulation of the BMP4-GPX4 pathway to protect RGCs and improve visual function through enhanced RSC differentiation.