Pigment epithelium-derived factor inhibits retinal and choroidal neovascularization

In this study, we investigated whether overexpression of pigment epithelium -derived factor (PEDF) by gene transfer can inhibit neovascularization by t esting its effect in three different models of ocular neovascularization. I ntravitreous injection of an adenoviral vector encoding PEDF resulted in ex pression of PEDF mRNA in the eye measured by RT-PCR and increased immunohis tochemical staining for PEDF protein throughout the retina. In mice with la ser-induced rupture of Bruch's membrane, choroidal neovascularization was s ignificantly reduced after intravitreous injection of PEDF vector compared to injection of null vector or no injection. Subretinal injection of the PE DF vector resulted in prominent staining for PEDF in retinal pigmented epit helial cells and strong inhibition of choroidal neovascularization. In two models of retinal neovascularization (transgenic mice with increased expres sion of vascular endothelial growth factor (VEGF) in photoreceptors and mic e with oxygen-induced ischemic retinopathy), intravitreous injection of nul l vector resulted in decreased neovascularization compared to no injection, but intravitreous injection of PEDF vector resulted in further inhibition of neovascularization that was statistically significant. These data sugges t that sustained increased intraocular expression of PEDF by gene therapy m ight provide a promising approach for treatment of ocular neovascularizatio n. (C) 2001 Wiley-Liss, Inc.