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MJ Tolentino, WT Wong, NJ Sund, Y Zeng, X Yang, AM Maguire, J Bennett; Adenoviral-VEGF Induced Pre-retinal and Optic Nerve Neovascularization in a Mouse. . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1277.
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Purpose: Intravitreal delivery of vascular endothelial growth factor (VEGF) has been shown to induce pre-retinal neovascularization in various animal models. Only few models have demonstrated optic disk neovascularization or pre-retinal neovascularization. The difficulty of producing these typical forms of retinal neovascularization may be related to the directionality of the VEGF gradient. Unlike the human condition where VEGF is produced in the inner retina, exogenously delivered VEGF originates from the vitreous. The purpose of this study is to test the hypothesis that overexpression of VEGF by adenovirus-CMV-VEGF infected retina can produce pre-retinal neovascularization and optic disk neovascularization in the mouse. Methods: Two microliters of Adenoviral -CMV- VEGF was injected into one eye of adult CD-1 mice while a control adenovirus, vehicle or PBS was injected into the contralateral eye. Animals were analyzed using high molecular weight fluorescein dextran flat mount, histopathology and confocal microscopy. Results: Fluorescein dextran flat mounts demonstrated pre-retinal neovascularization that originated from the retina or the optic nerve and grew out into the vitreous. The pre-retinal neovascularization as well as neovascularization of the disk were confirmed by hematoxylin and eosin staining and confocal microscopy. Control eyes did not demonstrate any neovascularization. Conclusion: Overexpression of VEGF by the retina can result in neovascularization of the optic nerve and pre-retinal neovascularization that resembles proliferative diabetic retinopathy with neovascularization of the disk and neovascularization elsewhere.
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