Experimental eye research最新文献

{"title":"Optimizing intracameral injection for targeted gene therapy and glaucoma model development","authors":"Shijiu Chen ,&nbsp;Lin Cong ,&nbsp;Xinlei Zhu ,&nbsp;Benxiang Qi ,&nbsp;Qingjun Zhou ,&nbsp;Weiyun Shi ,&nbsp;Bi Ning Zhang","doi":"10.1016/j.exer.2025.110408","DOIUrl":"10.1016/j.exer.2025.110408","url":null,"abstract":"<div><div>Intracameral injection is a widely used surgical technique in animal research, serving various purposes such as injecting microbeads to establish a glaucoma model, delivering adeno-associated virus (AAV) to transduce the trabecular meshwork or corneal endothelium, and administering drugs into the anterior chamber. However, performing intracameral injections in mice is particularly challenging due to the small size of the eye and the shallow anterior chamber. To prevent leakage of injected substances, traditional methods often involve the co-injection of sterile air or viscous agents. However, these approaches have significant drawbacks, including the need for repeated injections and the risk of repeated corneal injuries. To address these limitations, we developed a simplified intracameral injection technique for mice that minimizes tissue damage. In this method, the needle first enters the posterior chamber before passing through the pupil into the anterior chamber. To validate the efficacy and safety of this technique, we used it to deliver AAV into the anterior chamber for corneal endothelial cell transduction and to inject magnetic microbeads for establishing a glaucoma model. Our results demonstrate that this novel method is effective, reproducible, and associated with fewer complications.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"256 ","pages":"Article 110408"},"PeriodicalIF":3.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899012","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":"Vitreous proteomic insights into the pathogenesis of nonarteritic anterior ischemic optic neuropathy","authors":"Shuo Sun ,&nbsp;Yi Gong ,&nbsp;Dong Li ,&nbsp;Boshi Liu ,&nbsp;Qianhui Yang ,&nbsp;Manqiao Wang ,&nbsp;Wenqi Su ,&nbsp;Xiaomin Zhang ,&nbsp;Longli Zhang ,&nbsp;Rongguo Yu ,&nbsp;Xiaorong Li","doi":"10.1016/j.exer.2025.110407","DOIUrl":"10.1016/j.exer.2025.110407","url":null,"abstract":"<div><div>Non-arteritic anterior ischemic optic neuropathy (NAION) is a common cause of acute optic nerve injury and vision loss in older individuals. However, the pathogenesis of NAION remains poorly understood, and no treatment has conclusively demonstrated efficacy. This study aimed to explore and describe the proteome of the vitreous humor in eyes with NAION. Ten patients diagnosed with NAION and ten comparative controls diagnosed with idiopathic epiretinal membranes were enrolled in this study. The vitreous proteomes of both groups were analyzed using liquid chromatography-tandem mass spectrometry, and multiple reaction monitoring was performed to validate the target proteins. A total of 815 proteins were identified in both groups, of which 155 were common to both groups. Among these, 98 proteins were significantly upregulated and 57 proteins were downregulated in the NAION group compared to those in the controls. NAION is associated with the increased expression of proteins involved in hemostasis and metabolic pathways. Additionally, extracellular matrix (ECM) remodeling molecules were downregulated in the NAION vitreous, which likely reflects increased vitreous liquefaction and alterations in vitreous biomechanics. This study provides a comprehensive proteomic profile of the vitreous humor in eyes with NAION and highlights the dysregulation of hemostasis, metabolic pathways, and ECM remodeling. These findings enhance our understanding of the molecular mechanisms underlying NAION and may pave the way for the development of novel biomarkers and therapeutic targets.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"256 ","pages":"Article 110407"},"PeriodicalIF":3.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894311","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":"Comment on “Involvement of TGF-β signaling pathway-associated genes in the corneal endothelium of patients with Fuchs endothelial corneal dystrophy” by Nakagawa et al.","authors":"Sücattin İlker Kocamış,&nbsp;Bedia Kesimal","doi":"10.1016/j.exer.2025.110400","DOIUrl":"10.1016/j.exer.2025.110400","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"256 ","pages":"Article 110400"},"PeriodicalIF":3.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879334","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":"Profiling the Ocular Landscape of sEVs miRNAs: Mechanisms and Applications","authors":"Yifei Wu,&nbsp;Jiaqi Zhao,&nbsp;Xiaohe Lu","doi":"10.1016/j.exer.2025.110396","DOIUrl":"10.1016/j.exer.2025.110396","url":null,"abstract":"<div><div>In this review, we comprehensively discuss the application of sEVs miRNAs in ophthalmic diseases by examining their basic characteristics and clinical application potential. Initially, we provide an overview of sEVs, including their definition, source, and functions, while particularly highlighting the importance of miRNAs contained in sEVs and its prospects in the treatment of ocular diseases. Subsequently, the structure and composition of sEVs as well as the biological functions of their encapsulated miRNAs, which expands the current knowledge about their roles in ophthalmic physiology and pathology. In addition, the functions of sEVs miRNAs in the growth of ocular tissues, ocular tissue homeostasis, and common eye diseases such as glaucoma, age-related macular degeneration, and diabetic retinopathy, are discussed. The application potential of sEVs miRNAs as diagnostic biomarkers and drug delivery systems for ophthalmic conditions and therapeutic value in diverse eye diseases are explored. Finally, the current challenges affecting research in this field are outlined to provide a basis that guide future utilization of sEVs miRNAs in ophthalmic disease research and clinical management of diverse ophthalmological conditions.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"256 ","pages":"Article 110396"},"PeriodicalIF":3.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876931","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":"Investigating shared diagnostic genes and mechanisms between metabolic syndrome and dry eye disease via integrated bioinformatics analysis and in vivo validation","authors":"Ziyu Liu ,&nbsp;Yaqiong Li ,&nbsp;Jiayu Bao,&nbsp;Lei Tian,&nbsp;Ying Jie","doi":"10.1016/j.exer.2025.110374","DOIUrl":"10.1016/j.exer.2025.110374","url":null,"abstract":"<div><div>Recent research has established a bidirectional connection between metabolic syndrome (MetS) and dry eye disease (DED); however, the underlying mechanisms driving their co-occurrence remain poorly understood. This study employed bioinformatics and in vivo validation to investigate the shared diagnostic genes and underlying mechanisms linking MetS and DED. Differential expression analysis using Limma and weighted gene co-expression network analysis (WGCNA) identified 247 shared driver genes from MetS and DED cohorts. Functional enrichment analysis indicated that these genes are associated with immune regulation and inflammatory responses. Key diagnostic genes (Ccl5, Cxcr4, Ccl4, Spp1) were identified via PPI network analysis and validated using a receiver operating characteristic (ROC) curve. The MetS-DED mouse model further demonstrated CXCR4 overexpression in corneal epithelium and liver. These findings elucidate overlapping biomarkers and pathogenic pathways between MetS and DED, providing critical insights for advancing their diagnosis and therapeutic strategies.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"256 ","pages":"Article 110374"},"PeriodicalIF":3.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899011","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":"The association of trimethylamine N-oxide with diabetic retinopathy Pathology: Insights from network toxicology and molecular docking analysis","authors":"Jianping Gao,&nbsp;Jian Zhang,&nbsp;Lei Tang","doi":"10.1016/j.exer.2025.110399","DOIUrl":"10.1016/j.exer.2025.110399","url":null,"abstract":"<div><div>Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has emerged as a potential contributor to diabetic retinopathy (DR) progression. However, its molecular mechanisms in DR remain unclear. This study integrates network toxicology and multi-omics analyses to elucidate TMAO's role in DR pathogenesis. We identified TMAO-related targets through integration of CTD, SuperPred, and GeneCards databases. Differential expression analysis of DR-related genes was performed using GSE60436 and GSE102485 datasets. We intersected these with TMAO targets to identify key genes. Functional enrichment and pathway analyses were conducted, followed by immune cell infiltration assessment using ssGSEA. Machine learning algorithms (LASSO and RF) identified key marker genes, validated through GSE94019 dataset and in vitro experiments. Molecular docking explored interactions between TMAO and key proteins. We identified 45 TMAO-related targets implicated in DR. Functional analysis revealed enrichment in stress response and inflammatory pathways. Differential pathway analysis indicated significant upregulation of immune and apoptotic pathways in DR. Immune cell infiltration analysis showed increased levels of cytotoxic and inflammatory cells in DR. CASP3, CXCR4, and MAPK1 emerged as key marker genes, their expression significantly upregulated in PDR patients. Molecular docking highlighted stable interactions between TMAO and these proteins, suggesting potential modulation of their activity. TMAO-associated targets are enriched in inflammatory, oxidative, and apoptotic pathways in PDR tissues, suggesting a potential (but not causal) link to DR pathology. Our findings highlight the gut-retina axis in DR and provide a framework for targeting TMAO-mediated mechanisms in diabetic complications.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"256 ","pages":"Article 110399"},"PeriodicalIF":3.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902490","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":"Extracellular vesicles in the eye: from biomarkers and mediators of disease, to potential therapeutics","authors":"Ben Mead ,&nbsp;Dimitrios Karamichos","doi":"10.1016/j.exer.2025.110389","DOIUrl":"10.1016/j.exer.2025.110389","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110389"},"PeriodicalIF":3.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904579","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":"TCF4 expansion–associated loss of FN1 intron retention drives extracellular matrix accumulation in Fuchs endothelial corneal dystrophy","authors":"Soichiro Inagaki ,&nbsp;Taichi Yuasa ,&nbsp;Theofilos Tourtas ,&nbsp;Ursula Schlötzer-Schrehardt ,&nbsp;Friedrich Kruse ,&nbsp;Noriko Koizumi ,&nbsp;Naoki Okumura","doi":"10.1016/j.exer.2025.110398","DOIUrl":"10.1016/j.exer.2025.110398","url":null,"abstract":"<div><div>Fuchs endothelial corneal dystrophy (FECD), which is characterized by excessive extracellular matrix (ECM) accumulation and corneal endothelial cell degeneration, has trinucleotide repeat expansion in <em>TCF4</em> as a major genetic risk factor. While aberrant splicing has been implicated in FECD pathogenesis, the mechanistic link between splicing abnormalities and disease-specific features remains unclear. Here, we investigated the intron retention (IR) patterns in corneal endothelial cells from FECD patients with <em>TCF4</em> expansion. Initial RNA-Seq analysis using rMATS identified 486 upregulated and 89 downregulated IR events in expansion-positive FECD compared to controls. Subsequent analysis with the more stringent IRFinder algorithm revealed 10 upregulated IR events distributed across nine genes and, notably, 6 downregulated events exclusively localized within <em>FN1</em>, a major component of corneal guttae. While DEXSeq analysis showed reduced expression across <em>FN1</em> gene regions in FECD samples, subsequent qPCR validation in an independent cohort demonstrated significantly elevated <em>FN1</em> expression in both expansion-positive and expansion-negative FECD samples compared to controls. This paradoxical finding suggests that the loss of normal IR-mediated regulation may contribute to pathological <em>FN1</em> overexpression in FECD. Gene ontology analysis of IR-associated genes revealed enrichment in RNA splicing and ECM-related pathways, supporting a role for IR in disease pathogenesis. Our findings reveal an association between <em>TCF4</em> expansion and reduced <em>FN1</em> intron retention, which correlates with ECM accumulation, suggesting a potential link between RNA processing alterations and hallmark features of FECD. These results suggest that targeting IR-mediated regulation could represent a therapeutic strategy for preventing disease progression.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110398"},"PeriodicalIF":3.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859824","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":"Fluorometholone inhibits corneal epithelial proliferation, migration via targeting Rho GTPases: RhoA, Rac1, and Cdc42","authors":"Yong Lin ,&nbsp;Tianyi Xu ,&nbsp;Qiuruo Jiang,&nbsp;Jialu Chen,&nbsp;Hua Zhang,&nbsp;Peter Sol Reinach,&nbsp;Dongsheng Yan,&nbsp;Jia Qu,&nbsp;Shihao Chen","doi":"10.1016/j.exer.2025.110397","DOIUrl":"10.1016/j.exer.2025.110397","url":null,"abstract":"<div><div>Abnormal corneal epithelial hyperplasia is a common complication following refractive surgery. 0.1 % fluorometholone (FML) eye drops are commonly used for treatment. However, their efficacy varies among patients, potentially attributed to differences in the patient's microenvironment. The underlying reason remains incompletely understood. This study aimed to elucidate the molecular mechanisms of FML's action on corneal epithelial cells (CECs). The effects of FML on the cell viability, proliferation, cell cycle, and migration of human corneal epithelial cells (HCECs) were evaluated using MTS assay, EdU staining, flow cytometry, and scratch assay, respectively. Mouse corneal sections were immunofluorescently stained to assess cell proliferation. A corneal wound model, monitored by slit-lamp photography, was utilized to evaluate the impact of FML on wound healing. Gene expression alterations were detected via RNA sequencing. RT-qPCR and Western blot were employed to validate gene and protein expression in HCECs and mouse corneal epithelia. Proteomic analysis was conducted on tear samples from patients. FML treatment significantly inhibited CEC proliferation, migration, and wound healing. At the molecular level, FML treatment led to a remarkable downregulation of RhoA, Rac1, and Cdc42. Correspondingly, reductions in the downstream Erk and NF-κB signaling pathways were observed in both HCECs and mouse corneal epithelia. Moreover, these pathways were similarly downregulated in tear samples from clinical patients. In conclusion, FML inhibits CEC proliferation and migration by modulating the Rho GTPase signaling network, especially through RhoA/Rac1/Cdc42, thereby suppressing the Erk/NF-κB pathway.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"256 ","pages":"Article 110397"},"PeriodicalIF":3.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881442","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":"Reconstruction of highly and extremely aberrated wavefront for ocular Shack-Hartmann sensor using multi-task Attention-UNet","authors":"Yibin Tian ,&nbsp;Zipei Luo ,&nbsp;Dajiang Lu ,&nbsp;Cheng Liu ,&nbsp;Christine Wildsoet","doi":"10.1016/j.exer.2025.110394","DOIUrl":"10.1016/j.exer.2025.110394","url":null,"abstract":"<div><div>In certain ocular conditions, such as in eyes with keratoconus or after corneal laser surgery, Higher Order Aberrations (HOAs) may be dramatically elevated. Accurately recording interpretable wavefronts in such highly aberrated eyes using Shack-Hartmann sensor is a challenging task. While there are studies that have applied deep neural networks to Shack-Hartmann wavefront reconstructions, they have been limited to low resolution and small dynamic range cases. In this study, we introduce a multi-task learning scheme for High-Resolution and High Dynamic Range Shack-Hartmann wavefront reconstruction using a modified attention-UNet (HR-HDR-SHUNet), which outputs a wavefront map along with Zernike coefficients simultaneously. The HR-HDR-SHUNet was evaluated on three large datasets with different levels of HOAs (regularly, highly, and extremely aberrated), with successful reconstruction of all aberrated wavefronts, at the same time achieving significantly higher accuracy than both traditional methods and other deep learning networks; it is also computationally more efficient than the latter.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110394"},"PeriodicalIF":3.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870473","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}