期刊
JOURNAL OF NEUROCHEMISTRY
卷 80, 期 5, 页码 771-779出版社
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.0022-3042.2001.00737.x
关键词
aminoguanidine; diabetes; diabetic retinopathy; nitric oxide; nitrotyrosine; retinal cells
资金
- NEI NIH HHS [EY00300, P30EY11373] Funding Source: Medline
- NIDDK NIH HHS [DK57733] Funding Source: Medline
- NATIONAL EYE INSTITUTE [P30EY011373, R56EY000300, R01EY000300] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P01DK057733] Funding Source: NIH RePORTER
Aminoguanidine inhibits the development of retinopathy in diabetic animals, but the mechanism remains unclear. Inasmuch as aminoguanidine is a relatively selective inhibitor of the inducible isoform of nitric oxide synthase (NOS), we have investigated the effects of hyperglycemia on the retinal nitric oxide (NO) pathway in the presence and absence of aminoguanidine. In vivo studies utilized retinas from experimentally diabetic rats treated or without aminoguanidine for 2 months, and in vitro studies used bovine retinal endothelial cells and a transformed retinal glial cell line (rMC-1) incubated in 5 mm and 25 mm glucose with and without aminoguanidine (100 mug/mL). NO was detected as nitrite and nitrate, and nitrotyrosine and NOS were detected using immunochemical methods. Retinal homogenates from diabetic animals had greater than normal levels of NO and NOS (p < 0.05), and nitrotyrosine was greater than normal, especially in one band immunoprecipitated from retinal homogenates. Oral aminoguanidine significantly inhibited all of these increases. Nitrotyrosine was detected immunohistochemically only in the retinal vasculature of non-diabetic and diabetic animals. Retinal endothelial and rMC-1 cells cultured in high glucose increased NO and NT, and aminoguanidine inhibited both increases in rMC-1 cells, but only NT in endothelial cells. Hyperglycemia increases NO production in retinal cells, and aminoguanidine can inhibit this abnormality. Inhibition of diabetic retinopathy by aminoguanidine might be mediated in part by inhibition of sequelae of NO production.
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