Reduction of pathological retinal neovascularization, vessel obliteration, and artery tortuosity by PEDF protein in an oxygen-induced ischemic retinopathy rat model

Abstract

Retinopathy of prematurity (ROP) is a severe retinal disease in premature infants characterized by pathological neovascularization, obliteration of retinal vessels and increased vessel tortuosity. Currently, there are no completely satisfactory treatments for ROP. Pigment epithelium-derived factor (PEDF), a potent inhibitor of angiogenesis, appears late in gestation and its deficiency may be linked to development of ROP. This study investigates the preclinical efficacy of PEDF protein alone or in combination with VEGF antagonists for treating ROP. The safety of PEDF protein in the rat eye was assessed using functional in vivo measurements and histology. The efficacy of intravitreal injections (IVI) of various treatments was evaluated in a rat oxygen-induced retinopathy (OIR) model using in vivo imaging and flatmount analyses. No functional or histological side-effects were found in rat eyes after intravitreal PEDF protein injection. PEDF protein alone or combined with anti-VEGF drugs significantly reduced pathological neovascularization and vessel obliteration, comparable to the effects of anti-VEGF drugs alone. Regarding arterial tortuosity, treatment with a combination of PEDF, and VEGF antagonist was more effective than treatment with anti-VEGF alone. IVI of PEDF protein is safe. PEDF protein alone or combined with VEGF antagonists shows similar efficacy in reducing pathological neovascularization and vessel obliteration as anti-VEGF agents. Furthermore, only treatments involving PEDF protein, alone or with VEGF antagonists, significantly improved the quality of retinal vasculature. Thus, PEDF protein alone or combined with anti-VEGF agents presents a promising alternative to current anti-VEGF treatments for ROP.

Keywords: OIR rat model; PEDF protein therapy; ROP; angiogenesis; artery tortuosity; vessel obliteration.