{"title":"The role of microglia and complement C5/C5a in the pathogenesis of rhegmatogenous retinal detachment with choroidal detachment.","authors":"Huiyan Xu, Qiuhong Wang, Xuan Chen, Qingyu Huang, Shasha Xu, Zhifeng Wu","doi":"10.1016/j.csbj.2025.08.019","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Rhegmatogenous retinal detachment with choroidal detachment (RRDCD) is an uncommon and sight-threatening disorder marked by fast development and significant inflammation. This study aimed to identify cellular and molecular signatures distinguishing RRDCD from typical rhegmatogenous retinal detachment (RRD) and to investigate the roles of microglia and the complement C5/C5a pathway in disease pathogenesis.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) was employed to analyze vitreous samples from patients with RRD and RRDCD to characterize the cellular composition and molecular pathways. In vitro co-culture experiments were performed to investigate the functional impact of complement C5 on primary retinal microglia, and their subsequent effects on RF/6 A endothelial cells and ARPE-19 epithelial cells.</p><p><strong>Results: </strong>Our findings revealed a distinct cellular landscape in RRDCD, characterized by enhanced connectivity between microglia and dendritic cells, alongside a significant upregulation of the complement C5-C5AR1 interaction. In vitro experiments indicated that treatment with complement C5 enhanced microglial metabolic activity and activation, induced apoptosis in RF/6 A endothelial cells, and led to disruption of tight junction protein ZO-1 localization in ARPE-19 epithelial cells, suggesting a role in blood-retina barrier dysfunction.</p><p><strong>Conclusion: </strong>The findings substantiate the inflammatory hypothesis regarding the pathogenesis of RRDCD, emphasizing the critical functions of microglia and the complement C5/C5a pathway in intensifying retinal inflammation and undermining vascular integrity.</p>","PeriodicalId":10715,"journal":{"name":"Computational and structural biotechnology journal","volume":"27 ","pages":"3804-3813"},"PeriodicalIF":4.1000,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454608/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Computational and structural biotechnology journal","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.csbj.2025.08.019","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Rhegmatogenous retinal detachment with choroidal detachment (RRDCD) is an uncommon and sight-threatening disorder marked by fast development and significant inflammation. This study aimed to identify cellular and molecular signatures distinguishing RRDCD from typical rhegmatogenous retinal detachment (RRD) and to investigate the roles of microglia and the complement C5/C5a pathway in disease pathogenesis.
Methods: Single-cell RNA sequencing (scRNA-seq) was employed to analyze vitreous samples from patients with RRD and RRDCD to characterize the cellular composition and molecular pathways. In vitro co-culture experiments were performed to investigate the functional impact of complement C5 on primary retinal microglia, and their subsequent effects on RF/6 A endothelial cells and ARPE-19 epithelial cells.
Results: Our findings revealed a distinct cellular landscape in RRDCD, characterized by enhanced connectivity between microglia and dendritic cells, alongside a significant upregulation of the complement C5-C5AR1 interaction. In vitro experiments indicated that treatment with complement C5 enhanced microglial metabolic activity and activation, induced apoptosis in RF/6 A endothelial cells, and led to disruption of tight junction protein ZO-1 localization in ARPE-19 epithelial cells, suggesting a role in blood-retina barrier dysfunction.
Conclusion: The findings substantiate the inflammatory hypothesis regarding the pathogenesis of RRDCD, emphasizing the critical functions of microglia and the complement C5/C5a pathway in intensifying retinal inflammation and undermining vascular integrity.
期刊介绍：
Computational and Structural Biotechnology Journal (CSBJ) is an online gold open access journal publishing research articles and reviews after full peer review. All articles are published, without barriers to access, immediately upon acceptance. The journal places a strong emphasis on functional and mechanistic understanding of how molecular components in a biological process work together through the application of computational methods. Structural data may provide such insights, but they are not a pre-requisite for publication in the journal. Specific areas of interest include, but are not limited to:
Structure and function of proteins, nucleic acids and other macromolecules
Structure and function of multi-component complexes
Protein folding, processing and degradation
Enzymology
Computational and structural studies of plant systems
Microbial Informatics
Genomics
Proteomics
Metabolomics
Algorithms and Hypothesis in Bioinformatics
Mathematical and Theoretical Biology
Computational Chemistry and Drug Discovery
Microscopy and Molecular Imaging
Nanotechnology
Systems and Synthetic Biology
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
