Abstract
The purpose of this study was to investigate the effect of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin on oxygen-induced retinal neovascularization in the neonatal rat. Neovascularization was induced by maintaining Sprague-Dawley neonatal rats in 80% oxygen from birth to day 12 (P12), interrupted daily by 30 minutes in normal atmosphere, followed by a progressive return to 80% oxygen. On P12, the rats were placed in normal atmosphere. The rats were treated once daily with intraperitoneal injection of simvastatin (5 ml / kg body weight) or distilled water (C) from P6 to P17. The concentration of the simvastatin solution was 0.2 mg/ ml (H-SV) or 0.02 mg/ ml (L-SV) . On P18, 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. Neovascularization and AVAs in the retina were observed in oxygen-exposed animals, but not in control animals that remained throughout the experiments under normal atmosphere. The NV scores were 4.2 ± 0.7 in C (n=19), 4.3±0.7 in L-SV (n=21), and 5.3 ± 0.9 in H-SV (n=19) . There were no significant differences between C and L-SV and H-SV. The %AVAs were 19.7±3.7% in C (n=19), 18.2±4.2% in L-SV (n=21), and 16.6±3.8 % in H-SV (n=19) . VEGF concentrations were significantly inhibited by L-SV and H-SV treatments at 72hr (P15) after the end of oxygen exposure (p<0.05 for both) . These results indicate that simvastatin inhibited VEGF production at 72 hr after oxygen exposure, but did not reduce the NV score or % AVAs.
