The Role of Microglia and Complement C5/C5a in the Pathogenesis of Rhegmatogenous Retinal Detachment with Choroidal Detachment
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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, indicating its involvement in blood-retina barrier impairment.
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 promoted microglial proliferation and activation, induced apoptosis in RF/6A endothelial cells, and disrupted tight junctions 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.
