title: Oxidative stress promotes ocular neovascularization.
abstract: Mice deficient in superoxide dismutase 1 (Sod1(-/-) 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 SOD1 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 Sod1(-/-) compared to Sod1(+/+) mice. The compromised antioxidant defense system in Sod1(-/-) mice contributes to the pro-angiogenic environment, because treatment of Sod1(-/-) 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. J. Cell. Physiol. 219: 544-552, 2009. (c) 2009 Wiley-Liss, Inc.
authors.affiliation: Departments of Ophthalmology and Neuroscience, Johns Hopkins, University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Aling
authors.initials: A
authors.lastname: Dong
authors.forename: Bing
authors.initials: B
authors.lastname: Xie
authors.forename: Jikui
authors.initials: J
authors.lastname: Shen
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yokoi
authors.forename: Sean F
authors.initials: SF
authors.lastname: Hackett
authors.forename: Peter A
authors.initials: PA
authors.lastname: Campochiaro
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D020256:Choroidal Neovascularization / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007511:Ischemia / Q000150:complications / Q000188:drug therapy; D008268:Macular Degeneration / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015861:Retinal Neovascularization / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D012171:Retinal Vessels; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1