The ocular toxicity and pharmacokinetics of simvastatin following intravitreal injection in mice  

作　　者：Dennis Y.Tse Seong Jae Kim Inyoung Chung Feng He Theodore G.Wensel Samuel M.Wu 

机构地区：[1]Department of Ophthalmology,Baylor College of Medicine,Houston,TX 77030,USA [2]School of Optometry,the Hong Kong Polytechnic University,Hong Kong,China [3]Department of Ophthalmology,Institute of Health Sciences,College of Medicine,Gyeongsang National University,Jinju52727,Korea [4]Department of Biochemistry and Molecular Biology,BaylorCollege of Medicine,Houston,TX 77030,USA

出　　处：《International Journal of Ophthalmology(English edition)》2017年第9期1361-1369,共9页国际眼科杂志（英文版）

基　　金：Supported by the National Institute of Health under Award Number R01 EY004446&R01 EY019908;NIH Vision Core EY02520;the Retina Research Foundation(Houston),Research to Prevent Blindness Inc.;Hong Kong Polytechnic University grants G-UA7J and G-YBQT

摘　　要：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.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.

关 键 词：SIMVASTATIN RETINA ELECTRORETINOGRAPHY highperformance liquid chromatography electron microscopy intravitreal injection 

分 类 号：R77[医药卫生—眼科]