期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1991
卷号：88
期号：24
页码：11555-11558
DOI：10.1073/pnas.88.24.11555
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Retinal capillary closure induced by hyperglycemia is the principal pathophysiologic abnormality underlying diabetic retinopathy, but the mechanisms by which this induction occurs are not clear. Treatment of diabetic rats for 26 weeks with aminoguanidine, an inhibitor of advanced glycosylation product formation, prevented a 2.6-fold accumulation of these products at branching sites of precapillary arterioles where abnormal periodic acid/Schiff reagent-positive deposits also occurred. Aminoguanidine treatment completely prevented abnormal endothelial cell proliferation and significantly diminished pericyte dropout. After 75 weeks, untreated diabetic animals developed an 18.6-fold increase in the number of acellular capillaries and formed capillary microaneurysms, characteristic pathologic features of background diabetic retinopathy. In contrast, aminoguanidine-treated diabetic animals had only a 3.6-fold increase in acellular capillaries and no microaneurysms. These findings indicate that advanced glycosylation product accumulation contributes to the development of diabetic retinopathy and suggest that aminoguanidine may have future therapeutic use in this disorder.
