PTP4A3 contributes to pathological retinal neovascularization and vascular leakage partly through the PI3K-AKT signalling pathway.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus and an important cause of acquired blindness among working-age populations globally. Endothelial cell dysfunction is involved in the elevated diabetic retinal vascular leakage and pathological neovascularization. This study aimed to elucidate the impact of PTP4A3 in endothelial cell dysfunction in DR-related models. PTP4A3 expression was significantly increased in human diabetic retinopathy, and the streptozotocin-induced diabetic (STZ) model and oxygen-induced retinopathy (OIR) model. PTP4A3 overexpression led to excessive proliferation and migration of endothelial cell. Furthermore, PTP4A3 overexpression disrupted endothelial cell barrier function through decreasing Occludin and Claudin-5 expression. The PTP4A3 inhibitor reversed endothelial cell dysfunction induced by PTP4A3 overexpression in vitro, and ameliorated retinal vascular leakage and pathological neovascularization in vivo. Inhibition of PI3K or AKT partly alleviated endothelial cell dysfunction induced by PTP4A3 overexpression. Overall, PTP4A3 contributes to the enhanced proliferation, migration, and permeability of endothelial cells, which is associated with PI3K-AKT signaling pathway activation, thereby promoting retinal vascular leakage and pathological neovascularization.