Downregulation of PIK3IP1 in retinal microglia promotes retinal pathological neovascularization via PI3K-AKT pathway activation

Retinal pathological neovascularization involves endothelial cells, pericytes, photoreceptor cells, ganglion cells, and glial cells, whose roles remain unclear. Using the Scissor algorithm, we found that microglia are associated with formation of fibrovascular membranes and can promote pathological neovascularization. GO and KEGG results showed that PI3K-AKT pathway activation in retinal microglia was associated with pathological neovascularization, and PIK3IP1 was associated with retinal microglia activation. Then we used PCR, Western blot and Elisa techniques to confirm that the expression of VEGFA, FGF2, HGFα and MMP9 was increased in microglia after Lipopolysaccharide (LPS) induction. We also used cell flow cytometry and OIR models to verify the role of PI3K-AKT pathway and PIK3IP1 in microglia. Targeting of PIK3IP1 regulated the activation of the PI3K-AKT pathway in microglia, microglia function activation, and pro-angiogenic effects. These findings reveal the role of M1-type microglia in pathological neovascularization and suggests that targeting the PI3K-AKT pathway in microglia may be a new strategy for treating retinal pathological neovascularization.