CHARACTERIZATION OF NEOVASCULAR RESPONSES IN TRANSGENIC MICE WITH TISSUE–SPECIFIC OVEREXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR

Abstract

Abstract: : Purpose: To characterize transgenic mice with overexpression of vascular endothelial growth factor (VEGF) in photoreceptors for a model of diabetic retinopathy.Methods: Opsin–VEGF transgenic mice were examined by fundus fluorescein angiography and fluorescence microscopy after perfusion with fluorescence–labelled dextran (FITC–dextran). The flat mount preparations perfused with FITC–dextran were also incubated with rat monoclonal antibodies to mouse Ki–67 and CD105 for doubling labelling to identify proliferating cells and activated vascular endothelial cells during retinal neovascularization. Results:Fundus fluorescein angiography revealed both mild and severe proliferative retinopathy in opsin–VEGF transgenic mice. Fluorescence microscopy of FITC–dextran–perfused retinas demonstrated intraretinal microaneurysm and mild neovascularization in the deep capillary bed in mild cases, and massive development of retinal and/or subretinal neovascularization in severe cases. Histology further confirmed these vascular abnormalities. The severities of retinal neovascularization were well correlated with the number of cells expressing Ki–67 and CD105.Conclusions: Our opsin–VEGF transgenic mice present retinal neovascular changes similar to different stages of diabetic retinopathy, which are useful for development of new strategies for treatment of diabetic retinopathy.

Keywords: retinal neovascularization • transgenics/knock–outs • diabetic retinopathy