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Title: The ocular toxicity and pharmacokinetics of simvastatin following intravitreal injection in mice
Authors: Tse, DY 
Kim, SJ
Chung, I
He, F
Wensel, TG
Wu, SM
Keywords: Simvastatin
High-performance liquid chromatography
Electron microscopy
Intravitreal injection
Issue Date: 2017
Publisher: International Council of Ophthalmology
Source: International journal of ophthalmology, 2017, v. 10, no. 9, p. 1361-1369 How to cite?
Journal: International journal of ophthalmology 
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 mu mol/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 1.92-2.41 h. CONCLUSION: Intravitreal injection of up to 200 mu mol/L simvastatin produced no signs of adverse effects in the mouse retina. Simvastatin reaches the retina shortly after intravitreal injection and has a short half-life.
ISSN: 2222-3959
EISSN: 2227-4898
DOI: 10.18240/ijo.2017.09.05
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