The ocular toxicity and pharmacokinetics of simvastatin following intravitreal injection in mice
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Inyoung Chung. Department of Ophthalmology, College of Medicine, Gyeongsang National University, Jinju 52727, Korea. inyoung@gnu.ac.kr

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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., and Hong Kong Polytechnic University grants G-UA7J and G-YBQT.

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    Abstract:

    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. High-performance 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.

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Dennis Y. Tse, Seong Jae Kim, Inyoung Chung, et al. The ocular toxicity and pharmacokinetics of simvastatin following intravitreal injection in mice. Int J Ophthalmol, 2017,10(9):1361-1369

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Publication History
  • Received:September 07,2016
  • Revised:April 21,2017
  • Adopted:
  • Online: September 05,2017
  • Published: