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Inflammatory markers in nondiabetic and diabetic rat retinas exposed to ischemia followed by reperfusion.

Gustavsson C, Agardh CD, Hagert P, Agardh E

Unit on Vascular Diabetic Complications, Department of Clinical Sciences, Malmö University Hospital, Lund University, Malmö, Sweden. carin.gustavsson@med.lu.se

PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Published 9 April 2008 in Retina, 28(4): 645-52.
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