Oxidative Stress Promotes Ocular Neovascularization

Mice deficient in superoxide dismutase / (Sod I-/- mice) develop many features seen in patients with age-related macular degeneration (AMD) including choroidal neovascularization (NV). We sought to determine if the absence of SOD I contributes to the pro-angiogenic environment in the subretinal space or whether it is completely secondary to other changes in Bruch's membrane and the retinal pigmented epithelium (RPE) that precede the development of choroidal NV. In an ischemic retinopathy model or a transgenic model in which the rhodopsin promoter drives expression of vascular endothelial growth factor (VEGF) in photoreceptor there was significantly more NV in Sod I-/- compared to Sod I+/+ mice. The compromised antioxidant defense system in Sod I-/- mice contributes to the proangiogenic environment, because treatment of Sod I-/- mice with a mixture of antioxidants caused a significant reduction in ischemia-induced retinal NV. Wild-type mice treated with the same antioxidants also showed reduced ischemia-induced retinal NV, reduced VEGF-induced subretinal NV, and reduced choroidal NV at Bruch's membrane rupture sites. These data suggest that reactive oxygen species contribute to several types of ocular NV. This could explain why in the Age-Related Eye Disease Trial, antioxidant treatment reduced conversion from non-neovascular to neovascular AMD and severe vision loss, and suggest that potent antioxidants should be considered for other diseases complicated by ocular NV.