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P.L. Gehlbach, T. Deering, K. Callahan, M.E. Carrión, M.M. Hamilton, L.L. Wei, P.A. Campochiaro; Periocular Gene Product Delivery of Pigment Epithelium–derived Factor Induces Regression of Ocular Neovascularization. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):462.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate the hypothesis that periocular delivery of pigment epithelium–derived factor (PEDF) induces regression of established intraocular neovascularization. Periocular delivery of an adenovirus vector expressing the PEDF transgene (AdPEDF.11) is used to assess the effect of PEDF in murine models of retinal neovascularization (RNV) and choroidal neovascularization (CNV). Methods: Periocular delivery of AdPEDF.11, (an E1–/E3–/E4– vector expressing PEDF), AdNull.11, (an E1–/E3–/E4– null vector) or no injection were compared in transgenic mice that over–express vascular endothelial growth factor in the photoreceptors or in C57Bl/6 mice following laser rupture of Bruch’s membrane. Results: Significant regression of fourteen day old CNV (mean baseline area of each CNV = 0.038 mm2x10–3, n=65 CNV) was present 10 days following periocular delivery of AdPEDF.11, (mean area 0.020 mm2x10–3, n=77), (p=0.014). Growth rather than regression was present following AdNull.11 treatment (0.40 mm2x10–3, n=68) or no treatment (0.045 mm2x10–3, n=69). Significant regression of established RNV (mean area per eye = 0.196 mm2 x10–3, n=6) was present 7 days after periocular delivery of AdPEDF.11 (0.034 mm2 x10–3, n=8), (p= 0.021). Regression of established RNV was significantly greater in AdPEDF.11 treated eyes than in AdNull.11 treated eyes (0.118 mm2 x10–3, n=7), (p=0.009) and eyes receiving no treatment (0.088 mm2 x10–3, n=3), (p=0.0008). Conclusions: Periocular delivery of PEDF using the adenovirus vector AdPEDF.11 induces significant regression of established retinal and choroidal neovascularization in mouse models. Periocular gene transfer of PEDF may have therapeutic value in the setting of established retinal and choroidal neovascularization.
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