Role of pericytes in the blood-retinal barrier

Abstract

Pericyte dropout during breakdown of the blood？retinal barrier (BRB) is a major hallmark ofdiabetic retinopathy (DR), but it is unclear how pericyte dropout contributes to the progressionof DR. In this study, I show that PDGF-B/PDGFR$\beta$ signaling, which is essential for BRBbuildup in growing retinal vessels, is dispensable for maintaining BRB integrity in adult stableretinal vessels. Moreover, selective pericyte depletion in adult stable retinal vessels surprisinglydid not show phenotypes of BRB disintegration. However, the vessels became susceptible tobe leaky by external VEGF-A stimulus, which could be mediated by up-regulating vasculardestabilizing factors including Angiopoietin-2 and VEGFR2 through transcriptional activationof FOXO1 in unstable endothelial cells. Accordingly, either blocking Angiopoietin-2 oractivating Tie2 greatly ameliorated progression of BRB breakdown. Together, althoughpericyte coverage in quiescent endothelial cells is expendable, its impairment leaves themicroenvironment vulnerable to external stimuli that aggravate DR progression.