HMG–CoA REDUCTASE INHIBITOR( NK–104 ) ATTENUATES LEUKOCYTE–ENDOTHELIAL INTERACTION INDUCED BY ISCHEMIA–REPERFUSION INJURY IN THE RAT RETINA

Abstract

Abstract: : Purpose: Statins, 3–hydroxy–methylglutaryl coenzyme A reductase inhibitors, have been shown to lower serum cholesterol levels in clinical use. It is also reported that statins exert pleiotropic and beneficial effects on vascular endothelium. We investigated the effects of NK–104, one of the newly synthesized statins, on leukocyte accumulation during ischemia–reperfusion injury . Methods: Transient retinal ischemia was induced in Long Evans rats for 60 minutes using temporal ligation of the optic nerve. NK–104 was administered 5 minutes before the induction of retinal ischemia. Leukocyte–endothelial interactions in the post–ischemic retina were evaluated in vivo with a scanning laser ophthalmoscope. We evaluated the number of rolling leukocytes, the number of accumulated leukocytes and the diameters of major retinal artery and vein. P–selectin and intercellular adhesion molecule–1(ICAM–1) mRNA expression in the retina were semiquantitatively studied with RT–PCR method. Results:The NK–104 treated rats showed less arterial narrowing (66.8% P<0.05)compared with vehicle–treated rats. Venous dilation was inhibited in the NK–104 –treated rats (85.5% P<0.05)as compared to vehicle–treated rats. The number of the rolling leukocytes in the retinal veins of the NK–104 treated rats was reduced to 69.1% of vehicle–treated rats. The number of accumulated leukocytes in the NK–104 –treated rats was reduced to 68.7% of those in vehicle–treated rats. (P<0.05) The NK–104 treatment decreased ICAM–1 expression, while the treatment did not reduced P–selectin expression in the retina. Conclusions:NK–104 effectively attenuated ischemia–induced leukocyte–endothelial interactions in the rat retina after ischemia.

Keywords: retina