Choroidal neovascularization in the rat induced by adenovirus mediated expression of vascular endothelial growth factor

PURPOSE. TO determine the effects of an adenovirus vector encoding vascular endothelial growth factor(165) (Ad.VEGF) delivered to the subretinal space in the rat. METHODS. An El-deleted adenoviral vector encoding VEGF was injected into th e subretinal space of Long-Evans rats. Immunohistochemistry identified VEGF expression. Histopathologic changes in the retina were determined by light and electron microscopy, immunohistochemistry, fluorescein angiography, an d examination of wholemounts of choroid and retina. RESULTS. Increased expression of VEGF only in the retinal pigment epitheliu m (RPE) was detected after Ad.VEGF injection. Histopathology of these eyes revealed minimal subretinal exudation at 1 week followed by the appearance of vascular structures in the subretinal space by week 2, which persisted u p to 4 weeks. Shortening of photoreceptor outer segments and reduction of t he outer nuclear layer were present overlying areas of neovascularization. Fluorescein angiography of animals injected with fluorescein-dextran reveal ed a deep complex of new vessels. Choroidal flatmounts showed new vessel fo rmation, verified by detection of endothelial cells via immunohistochemistr y, arising from the choroid with absence of change in the overlying retinal vasculature. Electron microscopy confirmed the presence of sub-RPE endothe lial cells and pericytes and the loss of integrity of Bruch's membrane, and serial sectioning demonstrated choroidal vascular growth through Bruch's m embrane. CONCLUSIONS. These results support the hypothesis that overexpression of VE GF from RPE cells is capable of inducing choroidal neovascularization in th e rat and provide a framework for further examining angiogenic processes in the RPE- choroid complex.