Early Retinal Changes in a Neonatal Streptozotocin–Rat Model of Diabetes Type 2

Abstract

Abstract: : Purpose: Astrocytes and Muller cells appear to be important in the glial–endothelial integrity and balance of the blood–retinal barrier. We examined the presence of early glial and vascular retinal changes in a neonatal streptozotocin–rat model of diabetes type 2. Methods: Wistar rats were injected with streptozotocin (STZ) at the age of two days. Diabetic rats developed blood glucose levels >275 mg/dl two days after STZ injection. Four diabetic and four normal control animals were euthanized at 8, 12, 16 and 20 weeks. Wholemounts and cross sections of retinas were analyzed by immunofluorescence using glial fibrillary acidic protein (GFAP) antibody. Retinal digestion using tripsin was done for quantitative vascular morphometric analysis. Results: Flatmounts of the retina showed increased density of GFAP–positive cells, morphologically identical to astrocytes in STZ–diabetic rats after 8 weeks. Cross sections of the retina revealed that some GFAP–positive cells had the morphology and spatial organization of Muller cells. The morphometric analysis showed a significant difference between diabetic retinas and controls with regard to the ratio of the number of pericytes and number of endothelial cells per millimeter squared of capillary area. Conclusions: In this neonatal model of STZ–diabetic rats, hyperglycemia or its related changes altered GFAP expression shortly (8 weeks) after its development. The neonatal model of streptozotocin diabetic rat seems to be useful to evaluate the mechanisms of early retinal damage in type 2 diabetes, particularly in the period of time after puberty.

Keywords: diabetic retinopathy • retina • retinal glia