Kowluru Renu A
Kresge Eye Institute, Wayne State University, Detroit, MI 48201, USA.
Antioxid Redox Signal. 2005 Nov-Dec;7(11-12):1581-87. doi: 10.1089/ars.2005.7.1581.
Oxidative stress is increased in the retina in diabetes; the levels of oxidatively modified DNA and nitrosylated proteins are elevated, and antioxidant defense enzymes are impaired. The levels of superoxides are elevated in the retina, and the mitochondria become dysfunctional with proapoptotic protein, Bax, translocating from the cytosol into the mitochondria, and cytochrome c leaking out from the mitochondria. This is accompanied by increased retinal capillary cell apoptosis, and the formation of acellular capillaries and pericyte ghosts, the early signs of retinopathy in animal models of diabetic retinopathy. Inhibition of superoxides inhibits glucose -induced mitochondrial dysfunction, activation of caspase-3, and cell death in retinal capillary cells. In animal models, long-term administration of lipoic acid or other antioxidants inhibits the development of diabetic retinopathy via inhibition of accumulation of oxidatively modified DNA and nitrotyrosine and capillary cell apoptosis in the retina. Understanding the role of mitochondria in the development of retinopathy in diabetes should help identify therapies that can neutralize superoxides and inhibit their dysfunction and, ultimately, the development of retinopathy.
糖尿病患者视网膜中的氧化应激增加；氧化修饰的DNA和亚硝基化蛋白质水平升高，抗氧化防御酶受损。视网膜中超氧化物水平升高，线粒体功能失调，促凋亡蛋白Bax从细胞质转移到线粒体，细胞色素c从线粒体中泄漏。这伴随着视网膜毛细血管细胞凋亡增加，以及无细胞毛细血管和周细胞鬼影的形成，这是糖尿病性视网膜病变动物模型中视网膜病变的早期迹象。抑制超氧化物可抑制葡萄糖诱导的线粒体功能障碍、半胱天冬酶-3的激活以及视网膜毛细血管细胞死亡。在动物模型中，长期给予硫辛酸或其他抗氧化剂可通过抑制视网膜中氧化修饰的DNA和硝基酪氨酸的积累以及毛细血管细胞凋亡来抑制糖尿病性视网膜病变的发展。了解线粒体在糖尿病视网膜病变发展中的作用，应有助于确定能够中和超氧化物并抑制其功能障碍以及最终抑制视网膜病变发展的治疗方法。
