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J.G. Flannery, J. Lee, N. Walsh, I.R. Zolfaghar, V. Chiodo, C. Xia, X. Gong, W.W. Hauswirth; AAV2–Mediated Expression of Anti–Angiogenic Factors Inhibits Sub–Retinal Neovascularization in the VLDLR –/– Mouse . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5253.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We tested whether AAV–2 mediated delivery of PEDF, K1K3, Endostatin or the inhibitory domains of VEGF (exons 6 and 7), can decrease the growth and permeability of abnormal vessels in the VLDLR –/– mouse. Methods: To establish a pre–treatment baseline, fundus imaging and fluorescein angiography were performed at age P28, in both right and left eyes. The following day, 2ul of AAV2 vectors containing either PEDF, Endostatin, K1K3, exon–6 or exon–7 derived VEGF peptides were delivered via intravitreal injection to the right eye. Left eyes were treated with a PBS sham injection. Animals were followed up to age P180 and the effect of overexpression of the anti–angiogenic agents was determined by analysis of fluorescein angiography at 3, 6 and 10 weeks post– injection. Three–dimensional reconstructions of retinal flat mounts were performed following perfusion of animals with a lipophilic vessel dye, and quantitative measurements of vessel length and volume were computed from these reconstructions. Results: To control for the variable number of leaky foci between eyes, changes in vessel permeability with age, were represented as a ratio of the number of foci found at baseline (i.e. P27–29). Preliminary data suggest that each of the anti–angiogenic factors significantly reduces the number of leaky foci when compared to PBS treated control eyes. Conclusions:These five anti–angiogenic molecules when delivered via AAV significantly reduced retinal neovascularization in the VLDLR mutant mouse model. This gene delivery approach may prove useful for the treatment of other causes of retinal neovascularization in diabetic retinopathy and the wet from of age–related macular degeneration.
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