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S. Miyahara, J. Kiryu, K. Yamashiro, K. Miyamoto, K. Nishijima, F. Hirose, H. Tamura, H. Katsuta, Y. Honda; Simvastatin Attenuates Leukocyte Accumulation in the Retina of Streptozotocin-Induced Diabetic Rats . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3897.
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Purpose:Diabetic retinopathy is a major complication of diabetes, where leukocytes play an important role in the pathogenesis. Recently, simvastatin, a 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitor, has been reported to have various effects in addition to its lipid lowering ability. In the current study, we investigated the efficacy of simvastatin on diabetic change of retina in vivo. Methods:Diabetes was induced in male Long-Evans rats with streptozotocin injection. Simvastatin (25mg/kg/day) was administered orally for 2 weeks after diabetes induction. The numbers of leukocytes adhered to retinal vessel endothelium and leukocytes accumulated in the retinal tissue were counted. The expression of intracellular adhesion molecule-1 (ICAM-1) was evaluated with reverse transcription polymerase chain reaction. Results:Treatment with simvastatin reduced the numbers of adhered and accumulated leukocytes by 72.9 % (P<0.0001) and 41.0% (P=0.0005) compared with thevehicle-treated group, respectively. The expression of ICAM-1 was suppressed significantly in the retinas of simvastatin-treated group (P = 0.0067). Conclusions:Simvastatin suppressed leukocyte-endothelial interaction in diabetic retina via suppressing ICAM-1 expression on endothelial cells independent of its lipid lowering effects. These findings suggest that simvastatin should be further investigated as a treatment for diabetic retinopathy.
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