Ocular Hypothermic Conditioning Prevents Retinal Alterations Induced By Type 2 Diabetes Mellitus

SANDE PH; SALIDO EM; BORDONE M; GONZÁLEZ FLEITAS MF; CHIANELLI MS; KELLER SARMIENTO MI; DORFMAN D; ROSENSTEIN RE

Orlando

Congreso; ARVO Annual Meeting 2014; 2014

Purpose: Hypothermic conditioning protects the retina against acute ischemic injury. We have developed an experimental model of early type 2 diabetes mellitus (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 ocularhypothermic conditioning on the 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). Starting 3 weeks after STZ injection, retroocular temperature was weekly reduced to 32ºC for 20 min in one eye, while the contralateral eye was submitted to a sham procedure. At 12 weeks of treatment, fasting and postprandial glycemia, and glucose and insulin tolerance tests were analyzed. Retinal function (scotopicelectroretinograms(ERG)), retinal lipid peroxidation (thiobarbituric acid reactive substance levels), NOS activity (using 3H-arginine), TNFα (enzyme-linked immunosorbent assay), retinal morphology (optical microscopy), vascular endothelial growth factor(VEGF), and Müller cell glial fibrillary acidic protein (GFAP) levels (immunohistochemistry) were evaluated. Results: Animals which received a sucrose-enriched diet and STZ showed significant differences in metabolic tests, as compared with control groups. Weekly ocular hypothermia pulses which did not affect glucose metabolism in control or diabetic rats, prevented the decrease in the scotopicERG a-and b-wave, and oscillatory potential amplitude, and the increase in retinal lipid peroxidation, NOS activity, TNFα,VEGF,and Müller cell GFAP levels. Conclusions: These results indicate that ocular hypothermic conditioning can make the retina more tolerant against diabetic damage.