Combination of pigment epithelium derived factor with anti-vascular endothelial growth factor therapy protects the neuroretina from ischemic damage

Abstract

Ocular ischemia is a vision-threatening disease, and is a medical condition associated with many ocular diseases. Anti-VEGF therapy has limitations related to its side effects and suppression of physiological revascularization. Pigment epithelium derived factor (PEDF) has anti-angiogenesis and neurotrophic neuroprotective functions and is a promising agent in the treatment of ischemia-induced retinal neurodegeneration. The purpose of this study is to investigate the effect of PEDF and anti-VEGF and the combined therapy on the ischemic rat eye model ex vivo. In this study, the PEDF protein, anti-VEGF drug (Avastin) or the combination of PEDF and Avastin were intravitreally injected immediately after eye enucleation. Then the eyes were incubated in Dulbecco's modified eagle medium (DMEM) at 4 ℃ for 14 h. After that the eyes were fixed immediately by formalin. VEGF, PEDF and glial fibrillary acidic protein (GFAP) were detected by immunohistochemical (IHC) staining. The IHC staining intensity was evaluated for each eye. Compared to the groups treated by vehicle, PEDF, and anti-VEGF alone, the value of staining intensity of VEGF and GFAP was significantly reduced in the retina and choroidal vessels of the PEDF/Anti-VEGF treatment group. The intravitreally injected PEDF protein can locate in the retina and the choroidal vessels. Compared to the vehicle-treatment group, both the PEDF-treatment and the PEDF/Anti-VEGF treatment groups showed significantly decreased number of TUNEL-positive nuclei, and the PEDF/Anti-VEGF treatment group had the least TUNEL-positive nuclei. Combination of PEDF and an anti-VEGF drug (Avastin) is a possible therapeutic strategy against ischemic retinal and choroidal diseases.