Amelioration of Diabetes-Associated Abnormalities in the Vitreous Fluid by an Inhibitor of Albumin Glycation

被引：26

作者：

Cohen, Margo P. ^{[1
]}

Hud, Elizabeth ^{[1
]}

Wu, Van-Yu ^{[1
]}

Shearman, Clyde W. ^{[1
]}

机构：

[1] Glycadia Inc, Philadelphia, PA 19103 USA

来源：

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE | 2008年 / 49卷 / 11期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1167/iovs.08-1993

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

PURPOSE. Albumin modified by Amadori glucose adducts is a plasma-borne factor that activates cell signaling pathways, modulates the expression of growth factors and cytokines, and participates in the pathogenesis of microvascular complications of diabetes. In the present study, streptozotocin diabetic rats were treated with an orally administered compound that inhibits the nonenzymatic glycation of albumin to evaluate whether increased glycated albumin contributes to diabetes-associated abnormalities in the vitreous fluid. METHODS. Vitreous obtained from age-matched nondiabetic and streptozotocin-diabetic rats, half of which received the test compound 2-(3-chlorophenylamino) phenylacetic acid (23CPPA) by oral gavage for 26 weeks, was analyzed by immunoassay for pigment epithelium-derived factor (PEDF), vascular endothelial growth factor (VEGF) and glycated albumin content, by measurement of thiobarbituric acid reactive substances (TBARs) for lipid peroxide products and by colorimetric assay for hyaluronan content. RESULTS. Compared with that of nondiabetic controls, vitreous of diabetic rats contained decreased PEDF, increased VEGF, higher VEGF/ PEDF ratio, and elevated levels of TBARs, glycated albumin, and hyaluronan. These changes were significantly attenuated in rats treated with test compound despite the presence of marked hyperglycemia. CONCLUSIONS. Results indicate that inhibiting the formation of glycated albumin, which is increased in diabetes, ameliorates vitreous changes in angiogenic and metabolic factors associated with the development of diabetic retinopathy. The observed improvement in vitreous alterations associated with reductions in glycated albumin suggests that elevated levels of glycated albumin play a retinopathogenic role in diabetes that is operative and that can be therapeutically addressed independently of glycemic status. (Invest Ophthalmol Vis Sci. 2008; 49: 5089-5093) DOI: 10.1167/iovs.08-1993

引用

页码：5089 / 5093

页数：5

共 51 条

[1] Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor [J].