Article

Simvastatin inhibits leukocyte accumulation and vascular permeability in the retinas of rats with streptozotocin-induced diabetes.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
American Journal Of Pathology (impact factor: 4.89). 06/2004; 164(5):1697-706. DOI:10.1016/S0002-9440(10)63728-5
Source: PubMed

ABSTRACT Leukocytes play important roles in the pathogenesis of diabetic retinopathy. Recently, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have been reported to exert various effects in addition to their lipid-lowering ability. We investigated the effects of simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, on leukocyte-induced diabetic changes in retinas. Diabetes was induced in Long-Evans rats with streptozotocin, and simvastatin administration was begun immediately after the induction of diabetes. Two weeks of treatment with simvastatin suppressed significantly the number of leukocytes adhering to retinal vessel endothelium and the number of leukocytes accumulated in the retinal tissue by 72.9% and 41.0%, respectively (P < 0.01). The expression of intercellular adhesion molecule-1 (ICAM-1) and the CD18 (the common beta-chain of ICAM-1 ligands) were both suppressed with simvastatin. The amount of vascular endothelial growth factor in the retina was attenuated in the simvastatin-treated group. To evaluate the effects of simvastatin on leukocyte-induced endothelial cell damage, vascular permeability in the retina was measured with fluorescein-labeled dextran. Treatment with simvastatin markedly reduced retinal permeability (P = 0.014). This suggests that simvastatin attenuates leukocyte-endothelial cell interactions and subsequent blood-retinal barrier breakdown via suppression of vascular endothelial growth factor-induced ICAM-1 expression in the diabetic retina. Simvastatin may thus be useful in the prevention of diabetic retinopathy.

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Keywords

common beta-chain
 
diabetic retina
 
intercellular adhesion molecule-1
 
leukocyte-induced diabetic changes
 
leukocyte-induced endothelial cell damage
 
lipid-lowering ability
 
Long-Evans rats
 
reductase inhibitor
 
reductase inhibitors
 
retinal permeability
 
retinal tissue
 
retinal vessel endothelium
 
retinas
 
simvastatin administration
 
simvastatin attenuates leukocyte-endothelial cell interactions
 
simvastatin suppressed
 
simvastatin-treated group
 
subsequent blood-retinal barrier breakdown
 
vascular endothelial growth factor
 
vascular endothelial growth factor-induced ICAM-1 expression