Abstract
Abstract: :
Purpose:Pitavastatin, a novel 3–hydroxy–3–methylglutaryl coenzyme A reductase inhibitor, is known to be used as a therapeutic modality for hypercholesterolemia, but also has a reductive effect against ischemic stroke. The aim of this study was to examine pitavastatin prevents retinal ganglion cell (RGC) damage induced by N–Methyl–D–Aspartate (NMDA) injury or optic nerve axotomy. Methods: Fifty–six of adult Sprague–Dawley (SD) rat were used. Two types of injured models were prepared. In 30 rats, 20 nmol of NMDA was injected into the vitreous cavity, and optic nerve axotomy was performed in the others (n=26). Pitavastatin at the dose of 0.1, 1, 3 mg/kg had been orally administrated every day since 4 days before the injury until scarification (7 days after the NMDA injury or 10 days after the axotomy). To estimate the damage of RGCs, the number of retrogradely labeled RGCs with fluorogold was counted under microscopy. Results: Seven days after the NMDA injury, the number of RGCs is decreased to 1364.5 ± 102.9 cells/mm2 (n=6) against normal control of 2495 ± 105.3 (n=10, p<0.0001). Oral administration of pitavastatin rescued the number of RGCs from NMDA injury as 1266.3 ± 108.45 (1 mg/kg: n=8, p= 0.841), 1706.3 ± 108.45 cells/mm2 (3 mg/kg: n=6, p=0.011), respectively. As the same, ten days after the optic nerve axotomy, the number RGCs is also decreased to 505.6 ± 102.9 cells/mm2 (n=6), and pitavastatin rescue the RGCs from axotomy as 702.6 ± 183.4 (0.1 mg/kg: n=8, p= 0.0834), 819.3 ± 177.8 (1 mg/kg: n=6, p= 0.0426), and 1058.4 ± 212.9 cells/mm2 (1 mg/kg: n=6, p= 0.0002). Conclusions: Pitavastatin had neuroprotective effects against RGC damage induced by NMDA injury or optic nerve axotomy. Oral administration of pitavastatin may have potential therapeutic approach for the treatment of RGC injured diseases.
Keywords: neuroprotection • excitatory neurotransmitters • ganglion cells