Retinylamine Benefits Early Diabetic Retinopathy in Mice.

作者: Haitao Liu , Jie Tang , Yunpeng Du , Chieh Allen Lee , Marcin Golczak

DOI: 10.1074/JBC.M115.655555

关键词:

摘要: Recent evidence suggests an important role for outer retinal cells in the pathogenesis of diabetic retinopathy (DR). Here we investigated effect visual cycle inhibitor retinylamine (Ret-NH2) on development early DR lesions. Wild-type (WT) C57BL/6J mice (male, 2 months old when diabetes was induced) were made with streptozotocin, and some given Ret-NH2 once per week. Lecithin-retinol acyltransferase (LRAT)-deficient P23H mutant similarly studied. Mice euthanized after (WT Lrat−/−) 8 study to assess vascular histopathology, accumulation albumin, function, biochemical physiological abnormalities retina. Non-retinal effects examined leukocytes treated vivo. Superoxide generation expression inflammatory proteins significantly increased retinas or months, number degenerate capillaries albumin neural retina compared nondiabetic controls. Administration week inhibited capillary degeneration retina, reducing diabetes-induced superoxide proteins. also suppressed Lrat−/− mice. Leukocytes isolated from caused less cytotoxicity endothelial ex vivo than did control diabetics. lesions characteristic The constitutes a novel target inhibition DR.

参考文章(82)
Mamta Kanwar, Pooi-See Chan, Timothy S. Kern, Renu A. Kowluru, Oxidative damage in the retinal mitochondria of diabetic mice: possible protection by superoxide dismutase. Investigative Ophthalmology & Visual Science. ,vol. 48, pp. 3805- 3811 ,(2007) , 10.1167/IOVS.06-1280
Sanae Sakami, Tadao Maeda, Grzegorz Bereta, Kiichiro Okano, Marcin Golczak, Alexander Sumaroka, Alejandro J. Roman, Artur V. Cideciyan, Samuel G. Jacobson, Krzysztof Palczewski, Probing mechanisms of photoreceptor degeneration in a new mouse model of the common form of autosomal dominant retinitis pigmentosa due to P23H opsin mutations Journal of Biological Chemistry. ,vol. 286, pp. 10551- 10567 ,(2011) , 10.1074/JBC.M110.209759
M. Mizutani, C. Gerhardinger, M. Lorenzi, Müller cell changes in human diabetic retinopathy. Diabetes. ,vol. 47, pp. 445- 449 ,(1998) , 10.2337/DIABETES.47.3.445
H. P. Hammes, S. Martin, K. Federlin, K. Geisen, M. Brownlee, Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 88, pp. 11555- 11558 ,(1991) , 10.1073/PNAS.88.24.11555
Haruhisa Okawa, Alapakkam P. Sampath, Simon B. Laughlin, Gordon L. Fain, ATP Consumption by Mammalian Rod Photoreceptors in Darkness and in Light Current Biology. ,vol. 18, pp. 1917- 1921 ,(2008) , 10.1016/J.CUB.2008.10.029
Yunpeng Du, V. P. Sarthy, T. S. Kern, Interaction between NO and COX pathways in retinal cells exposed to elevated glucose and retina of diabetic rats American Journal of Physiology-regulatory Integrative and Comparative Physiology. ,vol. 287, ,(2004) , 10.1152/AJPREGU.00080.2003
Yunpeng Du, Casey M Miller, T.S Kern, Hyperglycemia increases mitochondrial superoxide in retina and retinal cells. Free Radical Biology and Medicine. ,vol. 35, pp. 1491- 1499 ,(2003) , 10.1016/J.FREERADBIOMED.2003.08.018
Johnny Tang, Timothy S. Kern, Inflammation in diabetic retinopathy. Progress in Retinal and Eye Research. ,vol. 30, pp. 343- 358 ,(2011) , 10.1016/J.PRETEYERES.2011.05.002
H. -P. Hammes, M. Brownlee, D. Edelstein, M. Saleck, S. Martin, K. Federlin, Aminoguanidine inhibits the development of accelerated diabetic retinopathy in the spontaneous hypertensive rat Diabetologia. ,vol. 37, pp. 32- 35 ,(1994) , 10.1007/BF00428774