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H. Takahashi, T. Nakazawa, H. Kudo, M. Tamai; Pitavastatin Prevents Leukocyte Recruitment to Retinal Tissue Following N–Methyl–D–Aspartate Injury . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1291.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To examine the response of NMDA on leukocyte recruitment in the rat retina and to explore the mechanism of neuroprotective effect of pitavastatin in retinal ganglion cells (RGCs). Methods: NMDA stimulation was performed by intravitreal administration of 20 nmol NMDA to adult Sprague–Dawley (SD) rats. Pitavastatin was administered orally at a dose of 3 mg/kg/day for 4 days prior to the injury and until the animal was sacrificed. FITC concanavalin A was perfused to visualize and count the leukocyte adhesion in the retinal vessel. The expressional changes of cytokines and adhesion related molecules were measured by quantitative PCR. The viability of RGCs was examined by TUNEL and the number of retrogradely labeled RGCs with fluorogold was counted. Results: The surviving RGCs was decreased to 54.9% of control (n=10, p<0.0001) following NMDA injury. Pitavastatin significantly prevented the loss of RGC to 68.7% of control compared to NMDA (n=6, p=0.011). The time course trial of leukocyte accumulation in the retinal vessel began at 3 hours, was still detected at 24 hours, and peaked at 9 hours after stimulation. The gene induction of cytokines including IL–1beta and TNFalpha, and leukocyte adhesion related molecules including P–, E–selectin, and integrin beta1 was detected by real–time PCR analysis. Pitavastatin prevented the accumulation of leukocyte significantly at 6 hours after NMDA injury (n=5, p=0.0454). Conclusions: NMDA increases the gene expression of proinflammatory cytokines and leukocyte adhesion molecules and induces the accumulation of leukocytes. Pitavastatin prevents the accumulation of leukocytes and has neuroprotective effects against NMDA–induced RGC damage. Oral administration of pitavastatin may have potential therapeutic approach for retinal diseases induced by exitotoxicity.
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