Inflammatory Markers in Nondiabetic and Diabetic Rat Retinas Exposed to Ischemia Followed by Reperfusion

Abstract

To examine the retinal inflammatory response to ischemia-reperfusion in nondiabetic and diabetic rats injected with either an omega-3-polyunsaturated fatty acid (docosahexaenoic acid [DHA]) or a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (pravastatin). Diabetes was induced by an intraperitoneal injection of streptozocin, and retinal ischemia was induced by ligation of the optic nerve and vessels, followed by reperfusion for 1 hour or 24 hours. Five minutes before surgery, an intravenous injection of DHA, pravastatin, or vehicle (ethanol) was administered. The mRNA expressions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, caspase-1, IL-1beta, P-selectin, vascular cellular adhesion molecule (VCAM)-1, and intercellular adhesion molecule (ICAM)-1 were compared between ischemic and nonischemic retinas as well as diabetic and nondiabetic nonischemic retinas. Ischemia induced increased expressions of TNF-alpha (P <or= 0.012), IL-1beta (P <or= 0.017), ICAM-1 (P <or= 0.025), and IL-6 (P = 0.012), and diabetes induced increased expression of caspase-1 (P <or= 0.046), VCAM-1 (P <or= 0.027), ICAM-1 (P <or= 0.016), IL-1beta (P = 0.016), and IL-6 (P = 0.041). Ischemia plus diabetes did not increase these findings significantly. DHA and pravastatin had some inhibitory effects in diabetic rats (P <or= 0.037). Inflammation triggered by ischemia-reperfusion may play a role in diabetic retinopathy. Intervention on lipid-based structures by omega-3-polyunsaturated fatty acids or statins seemed to have beneficial effects on inflammation in diabetes.