Pooja Nambiar , Aasef G. Shaikh , Palak Gupta , Jordan Murray , Fatema F. Ghasia
{"title":"Binocular dysfunction in Parkinson's Disease: Decoding near triad dynamics and divergence deficits","authors":"Pooja Nambiar , Aasef G. Shaikh , Palak Gupta , Jordan Murray , Fatema F. Ghasia","doi":"10.1016/j.exer.2025.110458","DOIUrl":"10.1016/j.exer.2025.110458","url":null,"abstract":"<div><div>Parkinson's Disease (PD) is a progressive neurodegenerative disorder that often affects the oculomotor system, causing strabismus and vergence impairments, particularly convergence insufficiency when focusing on nearby objects. This study evaluated eye deviation, vergence, accommodation, and pupil responses in PD during converging and diverging gaze shifts, correlating these findings with neurologic severity using the Unified Parkinson's Disease Rating Scale (UPDRS). We recruited 19 participants with varying severity of PD and 10 age-matched controls. 26 % of PD participants (PD Group 1) exhibited disparity-driven convergence and divergence responses comparable to controls, with expected miosis during convergence and mydriasis during divergence. In contrast, 74 % of PD participants (PD Group 2) showed reduced disparity-driven convergence and divergence, with diminished miosis during convergence and mydriasis during divergence. 37 % of PD participants exhibited increased exodeviation at near (30 cm) during binocular viewing in addition to reduced disparity-driven convergence. Blur-driven vergence was more significantly reduced than disparity-driven vergence in both PD participants and controls, likely due to presbyopia. Accommodation, assessed through changes in refractive error during disparity-driven and blur-driven vergence movements, was comparable between controls and PD patients. Our study indicates that PD disrupts disparity-driven convergence and divergence while sparing accommodation and blur-driven vergence. These findings offer insight into the pathophysiology of binocular dysfunction in PD, highlighting the involvement of neural structures such as the deep cerebellar nuclei and the supra-oculomotor area in vergence deficits and strabismus. Future studies can use these metrics to evaluate the effectiveness of targeted neuromodulation therapies in alleviating binocular dysfunction in PD.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110458"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Xu, Changkai Jia, Qiaocheng Qiu, Yuzhen Qin, Yuting Wang, Sijin Wu, Wei Li, Shengwei Ren, Yiqiang Wang
{"title":"NLRP3 proteins translocation into nuclei mediates SV40 T-antigen-induced corneal epithelial cell immortalization.","authors":"Jie Xu, Changkai Jia, Qiaocheng Qiu, Yuzhen Qin, Yuting Wang, Sijin Wu, Wei Li, Shengwei Ren, Yiqiang Wang","doi":"10.1016/j.exer.2025.110455","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110455","url":null,"abstract":"<p><p>NLRP3 proteins mainly act as inflammasome core components in cytosol, but was sparsely recorded to translocate into nuclei in some conditions, such as in human simplex virus (HSV)-infected corneas, in SV40 T-Ag-immortalized human corneal epithelial cell (HCEC) line, or during differentiation of naïve T cells. This study was designed to define whether or how SV40 T-Ag transfection per se caused NLRP3 translocation. It was demonstrated that infection of primary human corneal epithelial cells with lentivirus coding for SV40 T-Ag induced NLRP3 proteins' translocation into nuclei. Pull-down of NLRP3-containing complexes in HCEC nuclear proteins followed by mass spectrometry revealed 285 nuclear proteins interacting with NLRP3 proteins. Clustering analysis of these proteins showed that \"RNA binding\", \"Nucleocytoplasmic transport\" and \"Viral carcinogenic pathway\" were among the enriched molecular function terms or KEGG pathways. Structural modeling showed significant but differential affinities between NLRP3 proteins and histone subunits. Systemic Evolution of Ligands by EXponential enrichment (SELEX) was utilized to define DNA motifs potentially bound by NLRP3 proteins in vitro, and in-depth analysis of SELEXed motifs confirmed that the genes harboring those motifs were significantly associated with transcription and RNA processing. This study demonstrated that during the process of SV40 T-Ag-mediated corneal cell immortalization, NLRP3 proteins translocated into nuclei and behaved like a transcription factor. Besides confirming NLRP3 proteins' novel functions in non-immune cells or tissues like cornea, these findings also shed light on the mechanisms of virus-mediated immortalization or viral induced carcinogenesis.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110455"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chen Pengjie, Sun Yiming, Wu Han, Miao Qi, Xu Mingyu, Wang Jiawei, Xu Peifang, Ye Juan
{"title":"Multi-omics Analysis Reveals Lipid Metabolism Profiles and Regulatory Networks in Meibomian Glands Aging.","authors":"Chen Pengjie, Sun Yiming, Wu Han, Miao Qi, Xu Mingyu, Wang Jiawei, Xu Peifang, Ye Juan","doi":"10.1016/j.exer.2025.110457","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110457","url":null,"abstract":"<p><p>Aging is a significant risk factor for ocular surface diseases like meibomian gland dysfunction (MGD), which compromises tear film stability, leading to discomforts, visual impairment, and ocular structural damage. This study aims to elucidate the age-related changes in lipid metabolism and the regulation networks, providing insights into early pathogenic mechanisms and identifying potential molecular targets for preventing age-driven pathology in the MGs. We analyzed MGs from young (2 months) and aged (12 months) C57BL/6 mice using a multi-omics approach, transcriptomic analysis and lipidomic analysis. Our findings revealed shifts in lipid composition in aged MGs, especially with reduced phospholipid levels and elevated triglyceride (TG) levels. Differentially expressed genes (DEGs) in lipid metabolism were also identified, including glycerolipid, glycerophospholipid, and sphingolipid metabolism, forming a complex regulatory network of lipid metabolism. Some critical DEGs was validated by qPCR, confirming the upregulation of Akr1b8 (glycerolipid metabolism) and the downregulation of Mboat2 (glycerophospholipid metabolism), Degs2, and Sptlc3 (sphingolipid metabolism) in aged MGs. These findings highlighted lipid metabolism dysregulation as a key factor in age-related MGD, offering potential targets for future research to mitigate this condition and preserve ocular health.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110457"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Breaking barriers in ocular drug delivery for Uveitis: Advanced drug delivery systems, challenges and future prospects","authors":"Anju Ambekar, Jagannath Sahoo, Kavita Singh","doi":"10.1016/j.exer.2025.110456","DOIUrl":"10.1016/j.exer.2025.110456","url":null,"abstract":"<div><div>Uveitis is inflammation of the uvea, the middle layer of the eye which comprises of iris, ciliary body and choroid. Complications associated with uveitis include chronic pain, vision impairment and even blindness if not treated adequately. Conventional treatments for uveitis include immunosuppressive medications such as corticosteroids and biologics, which present challenges of low bioavailability due to complex anatomical structure of eye, rapid drug elimination, enzymatic degradation and the blood-retinal barrier. Consequently, they require frequent administration and are often associated with systemic side effects. In comparison to conventional drug delivery advanced drug delivery systems offer advantages such as targeted drug delivery, sustained drug release and reduction in side effects. A thorough literature search was conducted using Google Scholar, PubMed, covering publications from 2000 to 2024. The search terms included “uveitis,” “pathology and pathophysiology of uveitis,” “barriers in ocular drug delivery,” and “uveitis conventional treatments.” To refine the search results, “uveitis” was combined with different keywords such as “polymeric nanoparticles,” “liposomes,” “nanomicelles,” “dendrimers,” “nanoemulsions,” “hydrogels,” “implants,” or “microneedles” to gather information related to each novel drug delivery system. Only English language studies were considered. The inclusion criteria encompassed both review and research articles specifically related to uveitis, with a focus on studies evaluating novel drug delivery systems for its treatment. Studies on ocular drug delivery systems unrelated to uveitis were excluded. No formal statistical analysis was conducted. This review highlights various advanced drug delivery approaches including polymeric nanoparticles, liposomes, nanomicelles, dendrimers, nanoemulsions, hydrogels, implants and microneedles for the treatment of uveitis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"257 ","pages":"Article 110456"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Differential Analysis of Core Complement Components Expression and Localization Across Rodent, Non-Human Primate, and Human Ocular Tissues.","authors":"Aarin Jones, Aixu Sun, Hua Yang, Adrianna Latuszek, Nicole Negron, Peisheng Shi, Wen Fury, Guillermo L Lehmann, Ying Hu, Botir Sagdullaev","doi":"10.1016/j.exer.2025.110433","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110433","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is a leading cause of blindness. Genetic and pathophysiological studies have implicated that complement pathway dysfunction is a key contributor to progressive vision loss in AMD. Though the association between complement and AMD is recognized, numerous anti-complement therapeutics that had been tested in rodent model systems had limited success in clinical trials. Understanding complement factor production and site of action in ocular pathophysiology is critical for the development of efficacious therapeutics. However, our limited understanding of how these aspects of complement biology vary across species restricts our ability to predict clinical outcomes from studies using animal models. Here, we integrated transcriptomic and immunohistochemical assays to understand the expression and localization of core complement components (complement factor H (FH), complement 3 (C3), and complement 5 (C5)) between ocular tissues of rodent, non-human primate, and human species. We found that complement distribution varied significantly across the studied species, with the most striking differences observed in the FH. While rodents expressed Cfh, an alternative pathway inhibitor, mainly in the RPE, CFH expression in primate eyes was primarily confined to the choroid. These differences were consistent at the protein level, with rodent FH localized in the RPE and primate FH within the choriocapillaris, choroid and sclera. Regarding C5, a terminal complement pathway component, we observed minimal ocular mRNA levels in all three species. However, we observed detectable protein levels in the RPE in rodents and the choroid in humans. Next, C3 mRNA transcripts and C3 protein exhibited similar distribution in the choroid in both rodent and primate eyes. Together, our findings highlight key differences and similarities between rodent and primate complement biology that may offer insights into the translatability of animal models and inform the design of effective therapeutics.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110433"},"PeriodicalIF":3.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Susceptibility genes for allergic conjunctivitis revealed by cross-tissue transcriptome-wide association study","authors":"Qin Xu, Yiping Li, Xin Zhang","doi":"10.1016/j.exer.2025.110444","DOIUrl":"10.1016/j.exer.2025.110444","url":null,"abstract":"<div><div>Allergic conjunctivitis (AC) is a common immune-mediated ocular disorder, characterized by clinical manifestations such as ocular itching, conjunctival hyperemia, lacrimation, and mucoid discharge, which significantly impair patients' visual function and quality of life. Despite extensive research efforts devoted to uncovering the genetic predisposition to AC, the underlying pathogenic genes and molecular mechanisms remain incompletely understood, necessitating further research to elucidate its genetic basis. This study utilized AC data from the FinnGen R12 and incorporated expression quantitative trait loci data in the Genotype-Tissue Expression v8 database to perform a cross-tissue transcriptome-wide association study (TWAS). Analytical methods included functional summary-based imputation (FUSION), unified test for molecular signatures (UTMOST), and gene analysis combined with multi-marker genome annotation (MAGMA). To further validate the results, Mendelian randomization (MR) analysis and colocalization analysis were performed. Through TWAS and MAGMA analyses, 13 susceptibility genes associated with AC were identified. Following MR and colocalization analyses, three candidate genes—GAL3ST2, PDCD1 and TLR6—were ultimately selected and validated by FUMA tool, which may influence progression of AC by regulating pathways related to Toll-like receptor signaling. In conclusion, three susceptibility genes linked to the risk of AC were identified, providing new insights into the genetic mechanisms and potential pathogenic pathways underlying AC.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"257 ","pages":"Article 110444"},"PeriodicalIF":3.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"TRPV1 attenuates epithelial-mesenchymal transition via calpain-protein tyrosine phosphatase pathway in lens epithelial cells","authors":"Yosuke Nakazawa , Fuko Nishizawa , Sara Kawata , Yuki Sugiyama , Noriaki Nagai , Naoki Yamamoto , Megumi Funakoshi-Tago","doi":"10.1016/j.exer.2025.110435","DOIUrl":"10.1016/j.exer.2025.110435","url":null,"abstract":"<div><div>TRPV1, which is widely expressed throughout the body, is a non-selective cation channel activated by capsaicin. We previously reported that TRPV1 activation suppressed TGFβ2-induced epithelial-mesenchymal transition (EMT) by inhibiting Epidermal Growth Factor Receptor (EGFR) phosphorylation in lens epithelial cells (Sugiyama et al., 2021). However, the detailed molecular mechanism remains unclear. In this study, we focused on the calpain–protein tyrosine phosphatase (PTP) pathway to elucidate the detailed mechanism underlying TRPV1-induced EMT suppression. Calpain and PTP inhibitors mitigated the suppressive effect of capsaicin on TGFβ2-induced EMT <em>in vitro</em> and <em>ex vivo</em>. Finally, we shown that CalpainS1 and PTPN9 overexpression abrogated the effect of capsaicin on EMT in lens epithelial cells. Our findings indicate that calpain and PTP proteins are good candidates for preventing EMT after cataract surgery.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"258 ","pages":"Article 110435"},"PeriodicalIF":3.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wahab Hussain, Zhi-Liang Jiang, Yi Liu, Jia-Yi Wang, Talat Bilal Yasoob, Syed Ashiq Hussain, Umm E Laila, Dong-Dong Wu, Xin-Ying Ji, Ya-Long Dang
{"title":"PEST Proteolysis Signals Containing Nuclear Protein Related Proteins in Eye and Eye Diseases:A Review.","authors":"Wahab Hussain, Zhi-Liang Jiang, Yi Liu, Jia-Yi Wang, Talat Bilal Yasoob, Syed Ashiq Hussain, Umm E Laila, Dong-Dong Wu, Xin-Ying Ji, Ya-Long Dang","doi":"10.1016/j.exer.2025.110451","DOIUrl":"https://doi.org/10.1016/j.exer.2025.110451","url":null,"abstract":"<p><p>The human visual system is a critical component for understanding the world around us, but it is affected by various eye conditions that lead to visual impairments. More than 2.2 billion people worldwide suffer from vision problems such as macular degeneration, refractive errors, cataracts, and glaucoma. In the field of iridology, essential proteins for maintaining healthy eye activity are often mutated or dysregulated. Clear vision is essential for people, and mutations related to these proteins can significantly impact the prevalence and development of eye disorders. Proteins that are linked to ocular disorders, including the nuclear protein Ras, S-glutathionylation, the human ER1 protein, and the Pest Proteolysis Signal-containing Nuclear Protein (PCNP), were examined in this study. Identifying and studying potential treatment targets and strategies to regulate the function of these proteins is crucial for minimizing the prevalence of eye disorders. PCNP is specifically linked to the development of several eye disorders. The development of clinical strategies to effectively treat ocular disorders will benefit from an understanding of these molecular processes. The main focus of this study was on PCNP because of due to its significant role in the pathophysiology of eye disorders. Understanding the function of this protein is vital, as its dysregulation has been linked with several ocular diseases. It is important to fully understand the roles of these essential proteins to develop effective treatments and preventive measures for ocular problems. This review therefore aims to contribute to advancements in the research, treatment, and management of preventable blindness and vision impairment globally by influencing thoughts on how to target and regulate these prospective remedies.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110451"},"PeriodicalIF":3.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cassandra Warden , Dalton Raymond , Alex Sanchez , Mathew Seidel , Michael L. Risner
{"title":"Visualizing sphingomyelin in the retina","authors":"Cassandra Warden , Dalton Raymond , Alex Sanchez , Mathew Seidel , Michael L. Risner","doi":"10.1016/j.exer.2025.110446","DOIUrl":"10.1016/j.exer.2025.110446","url":null,"abstract":"<div><div>Sphingomyelin (SM) is a major component of cellular membranes that is altered by retinal and optic nerve degenerations. However, our understanding of the influence of SM during degenerations is hampered by methodological limitations. Prior investigations have demonstrated the accumulation of SM to plasma membranes of cultured cells, using an enhanced green fluorescent non-toxic truncated form of lysenin (EGFP-NT-Lys), which is a protein that specifically binds to SM. Here, we used EGFP-NT-Lys and a permeabilization-free method for immunohistochemistry, which preserves membrane integrity, to demonstrate the accumulation of SM to the plasma membranes of retinal ganglion cells (RGCs) and retinal endothelial cells (RECs) of the intact mouse retina. To determine the sensitivity and selectivity of EGFP-NT-Lys for SM and SM species, we performed lipid dot blot assays. We found EGFP-NT-Lys is highly selective for SM and preferentially binds to longer-chain SMs. We confirmed that EGFP-NT-Lys labeling of SM is modifiable by treatment with the catabolic enzyme, sphingomyelinase. In addition, we verified EGFP-NT-Lys binding to SM by competition assays and EGFP. Confocal image analysis of immunofluorescence of RGC and REC markers and EGFP-NT-Lys labeling in flat mount mouse retinas revealed SM heavily accumulates within the retinal vasculature and around the perimeter of RGCs. Our data demonstrates that EGFP-NT-Lys combined with a permeabilization-free method for immunohistochemistry can be used to detect and quantify plasma membrane associated SM in defined cells of the intact retina.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"257 ","pages":"Article 110446"},"PeriodicalIF":3.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chenyu Wu , Lujia Zhang , Qingge Guo , Ya Li , Ruiqi Qiu , Shun Yao , Bo Lei
{"title":"The pathogenicity of a novel frame-shift variant c.2321delC of PROM1 in an autosomal recessive cone-rod dystrophy pedigree may be associated with augment of autophagy","authors":"Chenyu Wu , Lujia Zhang , Qingge Guo , Ya Li , Ruiqi Qiu , Shun Yao , Bo Lei","doi":"10.1016/j.exer.2025.110453","DOIUrl":"10.1016/j.exer.2025.110453","url":null,"abstract":"<div><div><em>PROM1</em> gene mutations are increasingly recognized as significant contributors to inherited retinal diseases, demonstrating considerable heterogeneity in mutation loci and types. In our investigation of a Chinese pedigree presenting with autosomal recessive cone-rod dystrophy, we identified two compound heterozygous frame-shift variants of the <em>PROM1</em> gene: c.1645-1648del (p.K549Qfs∗3) and c.2321delC (p.A774Vfs∗2). We focused on elucidating the pathogenicity and underlying mechanisms of the novel c.2321delC variant. Following the American College of Medical Genetics and Genomics (ACMG) standards and guidelines, this novel variant was assessed as likely pathogenic. Cellular assays demonstrated that the mutated protein exhibited aberrant subcellular localization and decreased stability compared to wild-type counterparts. Notably, cellular models revealed significant autophagic activation evidenced by elevated LC3II/I ratios, while apoptosis markers remained unaffected. Despite preserved apoptotic pathways, the variant induced marked cellular viability impairment.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"257 ","pages":"Article 110453"},"PeriodicalIF":3.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}