Endothelial-pericyte interactions regulate angiogenesis via VEGFR2 signaling during retinal development and disease

Abstract

Pericytes stabilize the microvasculature by enhancing endothelial barrier integrity, resulting in functional networks. During retinal development, pericyte recruitment is crucial for stabilizing nascent angiogenic vasculature. However, in adulthood, disrupted endothelial-pericyte interactions lead to vascular dropout and pathological angiogenesis in ocular microvascular diseases, and strategies to stabilize the retinal vasculature are lacking. We demonstrate that direct endothelial-pericyte contact downregulates pVEGFR2 in endothelial cells, which enhances pericyte migration and promotes endothelial cell barrier function. Intravitreal injection of a VEGFR2 inhibitor in mouse models of the developing retina and oxygen-induced retinopathy increased pericyte recruitment and aided vascular stability. The VEGFR2 inhibitor further rescued ischemic retinopathy by enhancing vascularization and tissue growth while reducing vascular permeability. Our findings offer a druggable target to support the growth of functional and mature microvasculature in ocular microvascular diseases and tissue regeneration overall.