CONICET | Buscador de Institutos y Recursos Humanos

Diabetic retinopathy is a leading cause of acquired blindness in young, but also in elder adults, mostly affectedby type 2 diabetesmellitus (T2DM). The aim of this work was to develop an experimental model ofearly human T2DM in adult rats, and to analyze retinal functional, morphological, and biochemicalchanges arising during the early stages of the moderate metabolic derangement. For this purpose, animalswere divided in four groups: adult male Wistar rats receiving: tap water and citrate buffer i.p.(group 1), tap water with 30% sucrose and citrate buffer i.p. (group 2), tap water and 25mg/kg i.pstreptozotocin (STZ, group 3), or 30% sucrose and STZ (group 4). Fasting and postprandial glycemia, fructosamineand serum insulin levels were assessed. In addition, i.p. glucose and insulin tolerance testswere performed. Retinal function (electroretinogram, ERG) and morphology (optical microscopy), retinalnitric oxide synthase (NOS) activity (using 3H-arginine), lipid peroxidation (thiobarbituric acid reactivesubstances, TBARS), and TNFα levels (ELISA) were evaluated. At 6 and 12 weeks of treatment,animals which received a sucrose-enriched diet and STZ showed significant differences inmost metabolictests, as compared with the other groups. At 12 weeks of treatment, a significant decrease in the ERG aandb- wave and oscillatory potential amplitudes, and a significant increase in retinal NOS activity,TBARS, TNFα, glial fibrillary acidic protein in Müller cells, and vascular endothelial growth factor levelswere observed. These results indicate that the combination of diet-induced insulin resistance and aslight secretory impairment resulting from a low-dose STZ treatment mimics som