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 inj...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 200μmol/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 200μmol/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.展开更多
基金Supported by the National Institute of Health under Award Number R01 EY004446&R01 EY019908NIH Vision Core EY02520+1 种基金the Retina Research Foundation(Houston),Research to Prevent Blindness Inc.Hong Kong Polytechnic University grants G-UA7J and G-YBQT
文摘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 200μmol/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 200μmol/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.
