Increased Expression of VEGF in Photoreceptors and Superficial Retinal Capillaries Cause Severe Intraocular Neovascularization

Abstract

Purpose:: Increased expression of vascular endothelial growth factor (VEGF) in the photoreceptors is sufficient to stimulate sprouting of neovascularization from the deep capillary bed of the retina, but not the superficial retinal capillaries or the choriocapillaris. In this study, we investigated the effect of the increased VEGF expression in both the deep and superficial retina using transgenic mice with increased expression of human VEGF in photoreceptors (rho/VEGF transgenic mice) in the ischemia-induced retinal neovascvularization model.

Methods:: Rho/VEGF transgenic mice were used to investigate the effect of increased expression of VEGF in photoreceptor and superficial capillaries on the ischemic retinopathy model. The retinal neovascularization (NV) was assessed on P17 in rho/VEGF mice and C57BL6 control mice by histological examination and image analysis of flat mounts from mice perfused with fluorescein-labeled dextran. RT-PCR of P17 retinal RNA was performed using primers specific for murine VEGF.

Results:: Ischemia-induced retinal NV occurred in both rho/VEGF transgenic mice and C57BL/6 mice. In rho/VEGF transgenic mice, retinal NV was significantly more severe than in C57BL/6. RT-PCR showed that endogenous murine VEGF expression was increased in rho/VEGF transgenic mice significantly compared to controls.

Conclusions:: These data suggested that continuous increased expression of VEGF enhances hypoxia-induced retinal NV partly due to a significant increase in endogenous VEGF expression.

Keywords: retinal neovascularization • retinopathy of prematurity • transgenics/knock-outs