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A. Dong, B. Xie, K. Yokoi, S. F. Hackett, P. A. Campochiaro; Antioxidants Reduce Retinal and Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3445.
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Oxidative damage has been implicated in the pathogenesis of age-related macular degeneration (AMD). Mice deficient in superoxide dysmutase 1 (SOD1) have increased susceptibility to oxidative damage in the retina and develop a phenotype similar to that seen in patients with AMD including choroidal neovascularization (CNV). The purpose of this study was to investigate the role of SOD1 and SOD3 in the development of ocular neovascularization (NV).
Genetically engineered mice with altered expression of SOD1 or 3 (sod1-/-, sod3-/-, sod1 transgenic overexpressors, and sod3 transgenic overexpressors) were tested in models of ischemia-induced and VEGF-induced NV. Wild type mice were used in the same models to examine the effects of antioxidants.
Compared to littermate control mice, mice deficient in SOD1, but not those deficient in SOD3 nor those that over-express SOD1 or 3, showed a statistically significant 3-fold increase in ischemia-induced retinal NV. Rho/VEGF transgenic mice that were deficient in SOD1 showed a 3-fold increase in subretinal NV compared to rho/VEGF mice with normal levels of SOD1. Since SOD1 deficient mice have enhanced oxidative stress, we investigated the effects of antioxidants on NV. Compared to vehicle-treated controls, mice treated with a mixture of antioxidants (200mg/kg alpha-tocopherol, 250mg/kg ascorbic acid, and 100mg/kg alpha-lipoic acid) showed a significant reduction in ischemia-induced retinal NV, VEGF-induced subretinal NV in rho/VEGF transgenics, and laser-induced CNV.
These data suggest that oxidative stress creates a proangiogenic environment in the retina and choroid. These data may help to explain the reduced incidence of CNV in high-risk AMD patients taking antioxidants.
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