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K Mori, PL Gehlbach, A Ando, D McVey, L Wei, PA Campochiaro; Regression of Ocular Neovascularization by Increased Expression of Pigment Epithelium-Derived Factor . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3914.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Several pharmacologic treatments have been demonstrated to reduce ocular neovascularization when administered prior to the onset of angiogenic stimuli, but none have been shown to cause regression of already established ocular neovascularization. In this study, we tested the effect of adenoviral vector-mediated pigment epithelium-derived factor (PEDF) gene transfer on established neovascularization in transgenic mice with expression of vascular endothelial growth factor (VEGF) in photoreceptors (rho/VEGF mice), and in a model of choroidal neovascularization. Methods: Two weeks after the onset of VEGF transgene expression in rho/VEGF mice, or 2 weeks after laser-induced rupture of Bruch’s membrane in wild type mice, subgroups of mice were sacrificed and the baseline amount of neovascularization was measured by image analysis. The remainder of the mice received an intravitreous or subretinal injection of adenoviral vector containing a PEDF expression construct (AdPEDF.11) or control vector (AdNull.11). Results: Seven days after injection in rho/VEGF mice or 10 days after injection in the choroidal neovascularization model, the amount of neovascularization in AdPEDF.11-injected eyes was significantly less than the baseline level, indicating that regression of neovascularization had occurred. There was TUNEL staining within choroidal neovascular lesions in eyes injected with AdPEDF.11. Eyes given a subretinal injection of AdNull.11 had no TUNEL-positive cells within areas of choroidal neovascularization, although there was some detected elsewhere in the retina. Conclusion: These data indicate that increased expression of PEDF causes regression of ocular neovascularization by promoting apoptosis of cells within neovascular lesions. PEDF gene delivery may represent a new treatment paradigm for patients with established ocular neovascularization.
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