The role of microglia and complement C5/C5a in the pathogenesis of rhegmatogenous retinal detachment with choroidal detachment.

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.