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KC Behling, A Auricchio, EE O'Connor, AM Maguire, MJ Tolentino, JM Wilson, J Bennett; AAV-Mediated Retinal Transfer Of Anti-angiogenic Genes In A Murine Model Of Retinopathy Of Prematurity (ROP) . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2894.
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Purpose:Retinal neovascularization is a significant cause of morbidity and blindness. Anti-angiogenic factors have been shown to inhibit neovascularization and therefore may provide important therapies for ocular neovascular processes. We hypothesize that viral delivery of anti-angiogenic genes to retinal cells can result in inhibition of retinal neovascularization. Methods:Postnatal day (P) 3-5 C57Bl/6 mice were injected subretinally in one eye with one of the following adeno-associated viruses (AAV): AAV-PEDF, AAV-endostatin, or AAV-TIMP-3. Contralateral eyes were injected with a control virus containing the same promoter (CMV). From P7-P12, the mice were placed in a 75% oxygen environment after which time they were reared in room air [see IOVS 1994;35:101-11]. At P17-19 the extent of abnormal blood vessel growth was evaluated by angiography and histopathology. Transgene expression analyses confirmed expression of the relevant transgenes. Results:There was decreased neovascular pathology in eyes treated with each of the experimental vectors but not with the control vector. Conclusion:AAV-mediated delivery of any of a variety of anti-angiogenic genes can result in decreased neovascularization in a mouse model of ROP. This suggests that similar strategies may result in decreased retinal neovascularization in other neovascular pathologies of the eye such as diabetic retinopathy and choroidal neovascularization.
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