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H. Onda, Y. Hasebe, T. Nakanishi, T. Ueda, H. Yasuhara, R. Koide; The Effect of HMG-CoA Reductase Inhibitor Simvastatin on Oxygen-Induced Retinal Neovascularization in the Neonatal Rat . Invest. Ophthalmol. Vis. Sci. 2003;44(13):559.
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Purpose: HMG-CoA reductase inhibitor has been reported to both promote and to inhibit angiogenesis in vitro. The purpose of this study is to investigate the effect of HMG-CoA reductase inhibitor simvastatin on oxygen-induced retinal neovascularization in the neonatal rat. Methods: Neovascularization was induced by maintaining Sprague-Dawley (SD) neonatal rats in 80% oxygen for 11 days, interrupted daily by 30 minutes in room air followed by a progressive return to 80% oxygen. On experimental day 12, the rats were placed in room air. The rats were treated once daily with intraperitoneal injection of simvastatin (5mL/kg body weight) or distilled water (DW) from day 6 to 17. The concentration of the simvastatin solution was 0.2mg/ml (0.2S) or 0.02mg/ml (0.02S). Animals were divided into 6 groups, O2: in 80% oxygen (O2) with DW treatment (n=19), O2+0.2S: O2 with 0.2S treatment (n=19), O2+0.02S: O2 with 0.02S treatment (n=21), C: in room air with DW treatment (n=14), C+0.2S: C with 0.2S treatment (n=14), C+0.02S: C with 0.02S treatment (n=14). On day 18, the rats were sacrificed and the retinal samples were collected. Retinal neovascularization was scored and avascular areas of total retinal area (AVAs) were measured in ADPase stained retinas. A statistical analysis was performed using the ANOVA for NV and Mann-Whitney U-test for AVA. Results: Neovascularization and AVAs in the retina were observed in oxygen-exposed animals, but not in room air animals. The neovascularization scores were 4.21 in O2, 5.32 in O2+0.2S and 4.26 in O2+0.02S. AVAs were 19.7% in O2, 16.6% in O2+0.2S, and 18.2% in O2+0.02S. There were no significant differences between O2 and O2+0.2S, O2 and O2+0.02S. Conclusion: Simvastatin (0.2 or 0.02mg/ml) did not alter oxygen-induced neovascularization in neonatal rat retina.
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