● AIM: To investigate the retinal toxicity and pharmacokinetics of simvastatin intravitreally injected into mice. ● METHODS: Forty-eight 6-8-week-old C57BL/6J mice were used in this study. Simvastatin was intravitreally injected into the right eye of each mouse; the left eye was injected with vehicle and was used as a control. Bilateral dark-adapted electroretinography (ERG) was performed 1 and 7d following injection. Histology was examined using a combination of light, fluorescence and electron microscopy. Highperformance liquid chromatography (HPLC) was used to determine the decay in the retinal simvastatin concentration. ● RESULTS: ERG revealed no significant changes in the simvastatin-injected eyes compared to control. Histologic studies showed normal retinal morphology in eyes injected with simvastatin up to a final vitreal concentration of 200 μmol/L. No significant changes in the number of photoreceptors, bipolar cells or ganglion cells were found. The retinal simvastatin concentration decayed exponentially, with a half-life of 1.92-2.41h. ● CONCLUSION: Intravitreal injection of up to 200 μmol/L simvastatin produced no signs of adverse effects in the mouse retina. Simvastatin reaches the retina shortly after intravitreal injectionand has a short half-life.
- Electron microscopy
- Highperformance liquid chromatography
- Intravitreal injection
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