Inflammatory markers in nondiabetic and diabetic rat retinas exposed to ischemia followed by reperfusion.
OBJECTIVE
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.
Gustavsson
Carin
C
Unit on Vascular Diabetic Complications, Department of Clinical Sciences, Malmö University Hospital, Lund University, Malmö, Sweden. carin.gustavsson@med.lu.se
Agardh
Carl-David
CD
Hagert
Per
P
Agardh
Elisabet
E
D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D017035:Pravastatin / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D017035:Pravastatin