Dennis Y Tse1,2, Seong Jae Kim3, Inyoung Chung3, Feng He4, Theodore G Wensel4, Samuel M Wu1. 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, Jinju 52727, Korea. 4. Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
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.
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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