pitavastatin and Retinal-Diseases

Statins (3-hydroxy-methylglutaryl coenzyme A reductase inhibitors) have been shown to lower serum cholesterol levels in clinical use. Moreover, it has been reported that statins exert pleiotropic and beneficial effects on vascular endothelium. Therefore, we investigated the effects of pitavastatin, a new statin, on leukocyte accumulation during ischemia-reperfusion injury.. Transient retinal ischemia was induced in Long-Evans rats for 60 min by temporal ligation of the optic nerve. Pitavastatin (0.12, 0.35, or 1.1 mg/kg) was administered 5 min prior to the induction of retinal ischemia. Leukocyte-endothelial interactions in the post-ischemic retina were evaluated in vivo with acridine orange digital fluorography. The number of rolling leukocytes, number of accumulated leukocytes, and diameters of the major retinal artery and vein were evaluated. Intercellular adhesion molecule-1 (ICAM-1) mRNA expression in the retina was semiquantitatively studied using the RT-PCR method.. Pitavastatin-treated rats at doses of 0.35 and 1.1 mg/kg showed mild arterial narrowing (p < 0.01) and venous dilation (p < 0.01) compared with vehicle-treated (ischemic) rats. In rats treated with 0.35 mg/kg pitavastatin, the number of rolling leukocytes was significantly reduced by 35.5% (p < 0.01) 12 hr after reperfusion compared with that of vehicle-treated rats. With treatment at a dose of 0.35 mg/kg pitavastatin, the number of accumulated leukocytes was reduced to 68.7% (p < 0.01) 24 hr after reperfusion. Moreover, pitavastatin treatment significantly reduced ICAM-1 mRNA expression in the retina during ischemia-reperfusion injury.. Pitavastatin effectively attenuated ischemia-induced leukocyte-endothelial interactions in the rat retina.

Topics: Acridine Orange; Animals; Cell Communication; Endothelium, Vascular; Enzyme Inhibitors; Fluorescent Dyes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intercellular Adhesion Molecule-1; Leukocytes; Male; Quinolines; Rats; Rats, Long-Evans; Reperfusion Injury; Retinal Diseases; Retinal Vessels; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

To evaluate the neuroprotective effects of pitavastatin against neuronal retinal damage induced by ischemia-reperfusion injury in rats.. Ischemia-reperfusion injury was induced in Sprague-Dawley rats using ocular hypertension. Pitavastatin (0.1, 0.5, or 1.0 mg/kg) was given intravenously 12 hr or 5 min before, or 12 or 24 hr after the induction of ischemia-reperfusion injury. Morphometric and retrograde labeling analyses revealed neuroprotective effects when pitavastatin (0.5 mg/kg) was administered 5 min before--even 12 and 24 hr--after induction of ischemia-reperfusion injury. These effects depended on dose; protection was noted at pitavastatin concentrations of 0.5 and 1 mg/kg but not 0.1 mg/kg. Furthermore, preadministration of pitavastatin (0.5 mg/kg) reduced expression of P-selectin and intercellular adhesion molecule-1 at 12 and 24 hr after induction of ischemia-reperfusion injury.. As pitavastatin was efficacious in preventing retinal neuronal death, it may be a novel therapeutic modality for ischemic retinal diseases.

Topics: Animals; Cell Survival; Dose-Response Relationship, Drug; Enzyme Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Injections, Intravenous; Intercellular Adhesion Molecule-1; Male; Neuroprotective Agents; P-Selectin; Quinolines; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Retinal Diseases; Retinal Ganglion Cells; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors