Elham Norouz Dolatabadi , Mohammad Reza Akbarzadeh Zaky , Fatima Hashim Abbas , Amir Eftekhari Milani , Helder André , Effat Alizadeh
{"title":"Recent advances on modeling retinal disease: Towards efficient gene/drug therapy","authors":"Elham Norouz Dolatabadi , Mohammad Reza Akbarzadeh Zaky , Fatima Hashim Abbas , Amir Eftekhari Milani , Helder André , Effat Alizadeh","doi":"10.1016/j.exer.2025.110416","DOIUrl":"10.1016/j.exer.2025.110416","url":null,"abstract":"<div><div>Advanced modeling biotechnologies are required to understand retinal diseases and develop effective treatments based on the patient's genetic background, lifestyle, and environment. In this work, recent advances in different types of study models that are used in the retinal disease area of research will be explored. The retinal models to be covered are: <em>in vivo</em> systems (human and animal), <em>in vitro</em> organisms (cell lines, primary cells, patient-derived stem cells, microfluidics, organoids, and spheroids), ex vivo models (explant cultures and retinal tissue preparations), and in silico models (computational and mathematical). Moreover, the unique comprehension of models of retinal disease, advantages, and disadvantages will be scrutinized. Finally, innovations/improvements derived from models towards gene and pharmacological therapy that display promise for treating retinal illnesses are elucidated.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"256 ","pages":"Article 110416"},"PeriodicalIF":3.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143911953","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}
Yi Chen , Hanyue Xu , Lirong Xiao , Ming Zhang , Naihong Yan
{"title":"Single-cell RNA sequencing in the study of human retinal organoids","authors":"Yi Chen , Hanyue Xu , Lirong Xiao , Ming Zhang , Naihong Yan","doi":"10.1016/j.exer.2025.110417","DOIUrl":"10.1016/j.exer.2025.110417","url":null,"abstract":"<div><div>Single-cell RNA sequencing (scRNA-seq) has transformed the study of retinal development and diseases by enabling a detailed analysis of cellular diversity within retinal organoids (ROs). ROs generated from pluripotent stem cells mimic the essential characteristics of the human retina and provide a valuable <em>in vitro</em> model for investigating retinal development, cell interactions, and disease mechanisms. This review summarizes the application of scRNA-seq on RO research, emphasizing its capacity to identify distinct cell populations, uncover developmental trajectories, and reveal the molecular signatures of retinal diseases. scRNA-seq provides new insights into retinal neurogenesis, cellular diversity, and the pathophysiology of retinal degenerative diseases. This technology has enabled the identification of novel biomarkers and potential therapeutic targets. Integrating scRNA-seq with other technologies, such as spatial transcriptomics and CRISPR-based screening, can further deepen our understanding of retinal biology and improve treatment strategies.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"256 ","pages":"Article 110417"},"PeriodicalIF":3.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916795","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}
Shijiu Chen , Lin Cong , Xinlei Zhu , Benxiang Qi , Qingjun Zhou , Weiyun Shi , Bi Ning Zhang
{"title":"Optimizing intracameral injection for targeted gene therapy and glaucoma model development","authors":"Shijiu Chen , Lin Cong , Xinlei Zhu , Benxiang Qi , Qingjun Zhou , Weiyun Shi , 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}
Hassanain Qambari , Martin Hein , Chandrakumar Balaratnasingam , Paula Yu , Dao-Yi Yu
{"title":"Enabling visualization of GFAP-positive retinal glial cells, neurons and microvasculature in three-dimensions","authors":"Hassanain Qambari , Martin Hein , Chandrakumar Balaratnasingam , Paula Yu , Dao-Yi Yu","doi":"10.1016/j.exer.2025.110410","DOIUrl":"10.1016/j.exer.2025.110410","url":null,"abstract":"<div><div>Glial cells are one of the most numerous cell types in the vertebrate retina and they serve to support neurovascular function. The principal glial cell in the retina is the Müller cell, accounting for approximately 90 % of all retinal glial cells. Müller cells are phenotypically elongated in shape and were first described as ‘radial fibers’ by Heinrich Müller in 1851. Their structure spans the entire thickness of the retina, through all retinal layers from the internal to external limiting membrane. This unique three-dimensional spatial arrangement enables Müller cells' direct contact with almost all cell types in the retina to perform its function. Despite this, the current study of Müller cells has largely been limited to thin sections or in culture, which provide limited detail about its spatial arrangement and interconnection with other cell types. The novel technique described here enables the three-dimensional visualization of GFAP-positive Müller cell processes in rodent retina and is based on the isolated arterially perfused rat eye preparation. Our micro perfusion technique utilizes the microvasculature as the delivery channel to quickly and effectively preserve all retinal elements. Intravascular labelling enables visualization of the intact three-dimensional retinal microvasculature within its normal neuronal and glial confines. Additional immersion immunolabeling and subsequent clearing with RapiClear® enables the three-dimensional visualization of different retinal elements and their physical interaction. Volume rendering of confocal image stacks acquired from these specimens can facilitate the study of such interactions in normal and disease models to further our understanding. This technique may be replicated in human donor retinae for future investigations to provide insight into Müller cell form and spatial relationship with other cell types.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"257 ","pages":"Article 110410"},"PeriodicalIF":3.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975507","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}
Shuo Sun , Yi Gong , Dong Li , Boshi Liu , Qianhui Yang , Manqiao Wang , Wenqi Su , Xiaomin Zhang , Longli Zhang , Rongguo Yu , Xiaorong Li
{"title":"Vitreous proteomic insights into the pathogenesis of nonarteritic anterior ischemic optic neuropathy","authors":"Shuo Sun , Yi Gong , Dong Li , Boshi Liu , Qianhui Yang , Manqiao Wang , Wenqi Su , Xiaomin Zhang , Longli Zhang , Rongguo Yu , 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, 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, Jiaqi Zhao, 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}
Ziyu Liu , Yaqiong Li , Jiayu Bao, Lei Tian, Ying Jie
{"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 , Yaqiong Li , Jiayu Bao, Lei Tian, 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, Jian Zhang, 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 , 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}