Effects of Simvastatin on Retinal Structure and Function of a High-Fat Atherogenic Mouse Model of Thickened Bruch's Membrane
Effects of Simvastatin on Retinal Structure and Function of a High-Fat Atherogenic Mouse Model of Thickened Bruch's Membrane
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DOI：
10.1167/iovs.13-11636
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发表时间：
2014-01-01
影响因子：
4.4
通讯作者：
Luu, Chi D.
中科院分区：
文献类型：
--
作者：
Barathi, Veluchamy A.;Yeo, Sia W.;Luu, Chi D.
目的。为探讨他汀类药物(辛伐他汀)对增厚BM致高脂小鼠视网膜色素上皮(RPE)、膜(BM)及光感受器界面超微结构和功能的影响。方法将6周龄C57BL/6野生型C57BL/6小鼠按饮食和治疗方法分为3组：1组喂普通饲料，2组喂高脂饲料，3组喂喂高脂饲料，连续30周。对所有小鼠进行了30周的随访。在15周和30周的随访中，用眼底成像和视网膜电描记术检查视网膜形态和功能。结果：喂饲高脂饲料的小鼠的眼底图像显示出离散的、多个白斑的存在，而辛伐他汀治疗的小鼠眼底图像上的白斑明显减少了约73%。在高脂饲料喂养的小鼠，视网膜色素上皮的空泡增多，基底膜中有脂滴存在，基底膜弹力层增厚和碎裂，视网膜功能下降；这些超微结构和功能的改变在辛伐他汀治疗组得到显著改善。结论：长期服用辛伐他汀可显著改善高脂致动脉粥样硬化性增厚基底膜模型小鼠的RPE、基底膜和光感受器的超微结构和功能。
PURPOSE. To determine the effect of a statin (simvastatin) on the ultrastructure and function of the RPE, Bruch's membrane (BM), and photoreceptor interface in a high-fat atherogenic mouse model of thickened BM.METHODS. Wild-type C57BL/6 mice (6-weeks old) were divided into three study groups according to their diet and treatment given; Group 1, normal chow diet-fed mice; Group 2, high fat diet (HFD) fed mice; and Group 3, HFD-fed mice treated with simvastatin daily for 30 weeks. All mice were followed-up for 30 weeks. The retinal morphology and function was examined in vivo using fundus imaging and electroretinography at 15- and 30-weeks follow-up. At the end of the study, at 36 weeks of age, eye tissues were collected and retinal sections were examined using light microscopy and transmission electron microscopy.RESULTS. Fundus images of the HFD-fed mice showed the presence of discrete, multiple white spots, which was significantly reduced by approximately 73% in the simvastatin-treated animals. In the HFD-fed mice, there was an increase in the empty cytoplasmic vacuoles of the RPE, presence of lipid droplets in the BM, thickening and fragmentation of the elastic lamina of the BM, and a reduction in retinal function; these ultrastructural and functional changes were significantly improved in the simvastatin-treated group.CONCLUSIONS. Chronic administration of simvastatin significantly improves the ultrastructure and function of the RPE, BM, and photoreceptor in a high-fat atherogenic mouse model of thickened BM