TRANSGENIC MICE WITH INCREASED EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN THE RETINA - A NEW MODEL OF INTRARETINAL AND SUBRETINAL NEOVASCULARIZATION

Vascular endothelial growth factor (VEGF) has been implicated in retin al neovascularization (NV), but it has been difficult to produce retin al NV with exogenous VEGF. We investigated the effect of increased VEG T expression in the retina using tissue-specific, gain-of-function tra nsgenic mice in which the bovine rhodopsin promoter is coupled to the gene for human VEGF. Three founder mice were obtained and used to gene rate transgenic lines, One of the lines shows increased expression of VEGT in the retina by reverse transcription coupled to polymerase chai n reaction and Northern blots, and the VEGF is localized to photorecep tors by immunohistochemistry. These mice demonstrate new vessels origi nating front the deep capillary bed of the retina that extend beneath the photoreceptor layer into the subretinal space where they form clum ps of brood vessels surrounded by proliferated retinal pig-menten epit helial cells, The appearance is similar to subretinal NV seen in some patients, except that the blood vessels originate from the retinal vas culature rather than the choroidal vasculature, One of the other two l ines of mice did not shout increased expression of VEGF and did not ha ve NV the other line showed retinal degeneration, This study demonstra tes that overexpression of VEGF in the retina is sufficient to cause i ntraretinal and subretinal NV and provides a valuable new animal model .