Neuroprotective Effects of Pitavastatin, a Statin With High Affinity to Vascular Endothelium, Against Transient Retinal Ischemia

Abstract

Abstract: : Purpose: We have previously reported that statin, 3–hydroxy–3–methylglutaryl coenzyme A (HMGcoA) reductase inhibitor may exert neuroprotective effects by inhibiting leukocyte–endothelial interaction through the release of nitric oxide from the endothelium (Honjo et al., Arch Ophthalmol, 2002). The aim of this study was to evaluate the neuroprotective effects of pitavastatin, another statin withhigh affinity with vascular endothelium (so called vascular statin), against transient retinal ischemia. Methods: Transient retinal ischemia model was induced by ocular hypertension in Sprague–Dawley rats. P–selectin and intercellular adhesion molecule–1 (ICAM–1) gene expressions in the postischemic retina were studied with the aid of real–time polymerase chain reaction (RT–PCR). Histologic studies and retrograde labeling of retinal ganglion cells (RGCs) were carried out to evaluate retinal damage. Morphometric and analyses Results: Morphometric analysis revealed neuroprotective effects when pitavastatin (0.5 mg/kg) was administered 5 min before or 12 or 24 h after induction of ocular hypertension. The neuroprotective effects were observed in a dose–dependent manner. The neuroprotective effects against transient retinal ischemia was noted in experiments using pitavastatin at concentrations of 0.5 and 1 mg/kg, but not in those of 0.1 mg/kg. Also, pre–administration of pitavastatin (0.5 mg/kg) reduced expression of P–selectin and ICAM–1 at 12 and 24 h after induction of ocular hypertension. Conclusions: Because pitavastatin was efficacious in preventing retinal neuronal death, it may have application as a novel therapy for ischemic retinal diseases and glaucoma.

Keywords: ischemia • neuroprotection • vascular occlusion/vascular occlusive disease