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

Abstract

Purpose : Retinopathy of prematurity (ROP) is a worldwide severe disease which can lead to visual impairment or even blindness. It is characterized by retinal vessel obliteration, tortuous vessels and pathological neovascularization in the retina. The current treatments i.e. cryotherapy, laser ablation or a single intravitreal injection of anti-VEGF still produce limited effect and ineluctable complications. There is still a high medical need for alternative therapies.
Pigment epithelium-derived factor (PEDF), a potent angiogenesis inhibitor, appears late in gestation and it has been suggested that its lack may contribute to ROP.
Here we examined the effect of a single intravitreal injection of PEDF protein alone or in combination with anti-VEGF drugs and compared their efficacy in an oxygen-induced ischemic retinopathy (OIR) rat model.

Methods : We focused on angiogenesis parameters and on the quality of the retinal vasculature using in vivo imaging (scanning laser ophthalmoscopy/fluorescein angiography/optical coherence tomography (SLO/FA/OCT)) and ex vivo flatmounts analysis.

Results : PEDF protein alone or in combination with anti-VEGFs significantly suppressed the pathological neovascularization and reduced vessel obliteration as anti-VEGF drugs alone demonstrating that the treatment inhibited pathological neovascularization but not physiological angiogenesis. Importantly, PEDF protein alone or combined with an anti-VEGF drug significantly reduced the artery tortuosity indicating an improvement of the retinal vasculature quality.

Conclusions : PEDF protein alone or in combination with the anti-VEGF agents significantly reduced the pathological neovascularization and the vessel obliteration in the rat OIR model as did the anti-VEGF agents. Moreover, our PEDF protein alone or combined with anti-VEGF drugs was able to reduce the artery tortuosity indicating an improvement of the retinal vasculature quality. Thus, the use of PEDF protein alone or combined with anti-VEGF is beneficial and is a promising therapeutic for ROP.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.