A PEDF-derived peptide inhibits retinal neovascularization and blocks mobilization of bone marrow-derived endothelial progenitor cells

Abstract

Proliferative diabetic retinopathy is characterized by pathological retinal neovascularization, mediated by both angiogenesis (involving mature endothelial cells) and vasculogenesis (involving bone marrow-derived circulating endothelial progenitor cells (EPCs)). Pigment epithelium-derived factor (PEDF) contains an N-terminal 34-amino acid peptide (PEDF-34) that has antiangiogenic properties. Herein, we present a novel finding that PEDF-34 also possesses antivasculogenic activity. In the oxygen-induced retinopathy (OIR) model using transgenic mice that have Tie2 promoter-driven GFP expression, we quantified Tie2GFP(+) cells in bone marrow and peripheral blood by fluorescence-activated cell sorting (FACS). OIR significantly increased the number of circulating Tie2-GFP(+) at P16, correlating with the peak progression of neovascularization. Daily intraperitoneal injections of PEDF-34 into OIR mice decreased the number of Tie2-GFP(+) cells in the circulation at P16 by 65% but did not affect the number of Tie2-GFP(+) cells in the bone marrow. These studies suggest that PEDF-34 attenuates EPC mobilization from the bone marrow into the blood circulation during retinal neovascularization.