Early Retinal Changes in an Experimental Model of Type 2 Diabetes Characterized By Postprandial Hyperglycemia.

EZEQUIEL M. SALIDO; ARIAS P; SILBERMAN DAFNE M; RUTH E. ROSENSTEIN

Fort lauderdale, Florida

Congreso; ARVO 2011 visionary genomics; 2011

The association for research in vision and Ophthalmology ARVO

Invest Ophthalmol Vis Sci 2011;52: E-Abstract 5964.© 2011 ARVO 5964?A113 Early Retinal Changes in an Experimental Model of Type 2 Diabetes Characterized By Postprandial Hyperglycemia Ezequiel M. Salido, Sr., Pablo Arias, Dafne M. Silberman and Ruth E. Rosenstein Human Biochemistry, School of Medicine, University of Buenos Aires (UBA), C.A.B.A., Argentina Commercial Relationships: Ezequiel M. Salido, Sr., None; Pablo Arias, None; Dafne M. Silberman, None; Ruth E. Rosenstein, None Support: CONICET grant PIP1911 Abstract Purpose:Insulin resistance and altered insulin release are the pathogenetic mechanisms underlying the development of hyperglycemia in subjects with type 2 diabetes mellitus (T2DM). Microvascular complications, such as retinopathy, arise as a consequence of chronic hyperglycemia, eventually leading to blindness. Initially, the natural history of T2DM includes a period of normal or near-normal fasting plasma glucose levels and marked postprandial glycemic excursions. The impact of these glycemic spikes on retinal function is still matter of controversy. The aim of the present study was to develop a model of mild type 2 diabetes in rats (combining diet-induced insulin resistance and a slight β-cell secretory impairment) in order to study early retinopathic changes in rodents with slight fasting hyperglycemia and markedly elevated postprandial glucose levels. Methods:Adult male Wistar rats received tap water and citrate buffer i.p. (Group 1), tap water with 30% w/v sucrose and citrate buffer i.p. (Group 2), tap water and streptozotocin (STZ, 30 mg/kg i.p., Group 3), and 30% sucrose and STZ (Group 4). At 6 and 12 weeks of treatment fasting and postprandial glycemia, fructosamine and serum insulin levels were assessed. In addition, i.p. glucose and insulin tolerance tests were performed. Retinal function (scotopic ERGs), retinal morphology (optical microscopy), retinal lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and NOS activity (using 3H-arginine) were also evaluated. Results:At 6 and 12 weeks of treatment, animals of Group 4 showed significant differences in most metabolic tests as compared with the other groups. At 12 weeks of treatment, a significant decrease in the ERG a- and b- wave and oscillatory potential amplitudes, a significant increase in retinal TBARS levels, NOS activity, and glial fibrillary acidic protein in Müller cells were observed in Group 4. Conclusions:Only hyperglycemia resulting from the combination of a sucrose-enriched diet and STZ injection induced significant biochemical and functional retinal alterations. Keywords: diabetic retinopathy ? diabetes ? electroretinography: non-clinical © 2011, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.