Microglial phagocytosis involves hyperoxia-induced vessel regression in the neonatal retina

Oxygen concentration fluctuations are fundamental contributors to retinopathy of prematurity and other retinal neovascular diseases. However, the mechanism of retinal vascular regression under high oxygen stimulation remains unclear. In this study, we employed an oxygen-induced retinopathy mouse model to investigate the role of microglia in hyperoxia-induced vessel regression. Retinal vascular regression characteristics, microglial morphology, and localization were observed using immunofluorescence staining. Expression levels of phagocytic-related factors were analyzed via qPCR and Western blot techniques. Additionally, microglia were partially depleted to verify their functional contributions. TUNEL assay and RNA sequencing were performed to further explore the underlying mechanisms. Our findings indicated that central retinal vascular regression occurs rapidly at an early stage, accompanied by microglial migration and activation. Endothelial cell fragments were detected within microglia, confirming their involvement with phagocytic function, the upregulation of phagocytic-related factors further proved it. Notably, partial depletion of microglia significantly inhibited early retinal vascular regression and reduced endothelial cell apoptosis. Moreover, RNA sequencing and bioinformatics analysis revealed that microglial phagocytosis is regulated by the complement pathway. In conclusion, our study confirms the active participation of microglia in hyperoxia-induced retinal vascular regression through phagocytosis, thereby providing potential targets for early intervention in related diseases.