Overexpression of mitochondrial superoxide dismutase in mice protects the retina from diabetes-induced oxidative stress.
The retina experiences mitochondrial dysfunction in diabetes, superoxide levels are elevated, and mitochondrial superoxide dismutase (MnSOD) activity is decreased. Inhibition of superoxide accumulation in diabetes prevents mitochondrial dysfunction, apoptosis of retinal capillary cells, and the development of retinal histopathology. The purpose of this study is to examine the effect of overexpression of MnSOD on oxidative stress, DNA damage, and nitrative stress in the retina of diabetic mice. After 7 weeks of diabetes in MnSOD overexpressing (hemizygous) mice (MnSOD-Tg) and in their age-matched nontransgenic mice, parameters of oxidative stress and nitrative stress were measured in the retina. Overexpression of MnSOD prevented diabetes-induced decreases in retinal GSH levels and the total antioxidant capacity. In the same retina, MnSOD overexpression also inhibited diabetes-induced increases in the levels of 8-OHdG and nitrotyrosine. This suggests that MnSOD could be implicated in the pathogenesis of retinopathy by protecting the retina from increased oxidative damage experienced in diabetic conditions. Thus, understanding how changes in mitochondrial function result in the development of diabetic retinopathy could help identify SOD mimics to inhibit its development.
Kowluru
Renu A
RA
Department of Ophthalmology, Kresge Eye Institute, Wayne State University, Detroit, MI 48201, USA. rkowluru@med.wayne.edu
Kowluru
Vibhuti
V
Xiong
Ye
Y
Ho
Ye-Shih
YS
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D012160:Retina / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D013482:Superoxide Dismutase