THERAPEUTIC EFFICACY OF MELATONIN IN REDUCING RETINAL DAMAGE IN AN EXPERIMENTAL MODEL OF EARLY TYPE 2 DIABETES IN RATS

ROSENSTEIN R; BORDONE MP; CHIANELLI, MONICA; KELLER SARMIENTO, MARIA; DORFMAN D; MIRANDA M; SALIDO E

Seattle

Congreso; The Association For Research In Vision And Ophthalmology (Arvo); 2013

The Association For Research In Vision And Ophthalmology (Arvo) 2013

Abstract Purpose:Diabetic retinopathy is a leading cause of acquired blindness in adults, mostly affected by type 2 diabetes mellitus (T2DM). We have developed an experimental model of early T2DM in adult rats by combining diet-induced insulin resistance and a slight β-cell secretory impairment, which mimics some features of human T2DM at its initial stages, and provokes significant retinal alterations. The aim of the present work was to analyze the effect of melatonin on retinal changes induced by a moderate metabolic derangement. Methods:Adult male Wistar rats received a control diet or 30% sucrose in the drinking water ad libitum. Three weeks after this treatment, animals were injected with vehicle or streptozotocin (STZ, 25 mg/kg). One day after vehicle or STZ injection, animals were subcutaneously implanted with a pellet of melatonin, which was replaced every 15 days. At 12 weeks of treatment, fasting and postprandial glycemia, and glucose and insulin tolerance tests were analyzed. Retinal function (scotopic elctroretinograms), retinal lipid peroxidation (thiobarbituric acid reactive substance levels), NOS activity (using 3H-arginine), TNFα (enzyme-linked immunosorbent assay), retinal morphology (optical microscopy), and Müller cells glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor levels (VEGF) (immunohistochemistry) were evaluated. Results:Animals which received a sucrose-enriched diet and STZ showed significant differences in metabolic tests, as compared with control groups. Melatonin, which did not affect glucose metabolism in control or diabetic rats, prevented the decrease in the electroretinogram a-and b-wave, and oscillatory potential amplitude, and the increase in retinal lipid peroxidation, NOS activity, TNFα and Müller cell GFAP and VEGF levels. Conclusions:These results indicate that melatonin protected the retina from the alterations observed in an experimental model of diabetic retinopathy associated with type 2 diabetes. Keywords: 590 melatonin ? 499 diabetic retinopathy ? 637 pathology: experimental