Downregulation of vascular endothelial growth factor and integrinβ3 by endostatin in a mouse model of retinal neovascularization

Retinal neovascularization is among the leading causes of vision impairment throughout the world. Intraocular expression of vascular endothelial growth factor (VEGF), an angiogenic protein, and integrins, a group of cell adhesion molecules, is closely correlated with neovascularization in such neovascular diseases. The purpose of this study is to determine the effect of endostatin, a potent anti-angiogenic factor, on gene expression of vascular endothelial growth factor (VEGF) and intearin beta(3) in a mouse model of oxygen-induced retinopathy. C57BL/6 mice were given intravitreous injections of 1.0 mu g endostatin at P-12. At P-17, retinal VEGF and integrin beta(3) mRNA levels were measured by real-time quantitative PCR in the hyperoxia mice and in the endostatin-treated mice. Analysis of 12 separate experiments revealed a 3.5-fold decrease in VEGF levels between hyperoxia mice and endostatin-treated mice (p<0.01) and a 2.5-fold decrease in integrin 3 levels between hyperoxia mice and endostatin-treated mice (p <0.01). These data suggest that intraocular expression of VEGF and integrin beta(3) mRNA is down-regulated by endostatin, which may provide a new therapeutic approach for ocular neovascularization. (C) 2005 Published by Elsevier Ltd.