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Vascular endothelial growth factor (VEGF) has been implicated in retinal neovascularization (NV), but it has been difficult to produce retinal NV with exogenous VEGF. We investigated the effect of increased VEGF expression in the retina using tissue-specific, gain-of-function transgenic mice in which the bovine rhodopsin promoter is coupled to the gene for human VEGF. Three founder mice were obtained and used to generate transgenic lines. One of the lines shows increased expression of VEGF in the retina by reverse transcription coupled to polymerase chain reaction and Northern blots, and the VEGF is localized to photoreceptors by immunohistochemistry. These mice demonstrate new vessels originating from the deep capillary bed of the retina that extend beneath the photoreceptor layer into the subretinal space where they form clumps of blood vessels surrounded by proliferated retinal pigmented epithelial …