Overexpression of vascular endothelial growth factor (VEGF) in the retinalpigment epithelium leads to the development of choroidal neovascularization

Vascular endothelial growth factor (VEGF) has been strongly implicated in t he development of choroidal neovascularization found in age-related macular degeneration. Normally expressed In low levels, this study investigates wh ether the overexpression of VEGF in the retinal pigment epithelium is suffi cient to cause choroidal neovascularization in the rat retina. A recombinan t adenovirus vector expressing the rat VEGF(164) cDNA (AdCMV.VEGF) was cons tructed and injected into the subretinal space. The development of neovascu larization was followed by fluorescein angiography, which indicates microva scular hyperpermeability of existing and/or newly forming blood vessels, an d histology. VEGF mRNA was found to be overexpressed by retinal pigment epi thelial cells and resulted in leaky blood vessels at 10 days postinjection, which was maintained for up to 31 days postinjection, By 80 days postinjec tion, flew blood vessels had originated from the choriocapillaris, grown th rough the Bruch's membrane to the subretinal space, and disrupted the retin al pigment epithelium. This ultimately led to the formation of choroidal ne ovascular membranes and the death of overlying photoreceptor cells. By cont rolling the amount of virus delivered to the subretinal spare, we were able to influence the severity and extent of the resulting choroidal neovascula rization. These results show that even temporary overexpression of VEGF in retinal pigment epithelial cells is sufficient to induce choroidal neovascu larization in the rat eye.