The Effects of Metformin on Obesity-Induced Dysfunctional Retinas.
The Effects of Metformin on Obesity-Induced Dysfunctional Retinas.
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DOI：
10.1167/iovs.16-20691
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发表时间：
2017-01-01
影响因子：
4.4
通讯作者：
Ko GY
中科院分区：
文献类型：
--
作者：
Kim AJ;Chang JY;Shi L;Chang RC;Ko ML;Ko GY
本研究的目的是确定二甲双胍对肥胖诱导的2型糖尿病小鼠视网膜功能障碍的影响。本研究采用高脂饮食（HFD）诱导的糖尿病小鼠模型（C57 BL/6 J）。HFD方案2个月后，HFD小鼠通过经口灌胃每日给予二甲双胍。定期监测体重、葡萄糖耐量和视网膜光反应。用荧光素血管造影（FA）评估视网膜血管的变化。收获眼组织（视网膜、玻璃体和透镜）并分析分子变化，如通过免疫荧光染色、蛋白质印迹分析和细胞因子谱确定的。从饮食方案后1个月开始，喂食HFD的小鼠具有轻度受损的视网膜光反应，如通过视网膜电图（ERG）测量的，其与对照相比随时间恶化。在接受二甲双胍治疗的HFD小鼠中，全身葡萄糖水平恢复正常，体重增加减缓。二甲双胍可逆转HFD诱导的视网膜磷酸化蛋白激酶B（pAKT）、细胞外信号调节激酶（pERK）和5′ AMP活化蛋白激酶（pAMPK）的变化。然而，二甲双胍治疗3个月并没有恢复视网膜光反应，也没有减轻HFD诱导的视网膜新生血管形成，即使它确实减少了眼内炎症。虽然二甲双胍能够逆转HFD诱导的全身变化，但不能恢复HFD引起的视网膜光反应或阻止新生血管形成。
The purpose of this study was to determine the effects of metformin on dysfunctional retinas in obesity-induced type 2 diabetic mice. A high-fat diet (HFD)-induced diabetic mouse model (C57BL/6J) was used in this study. After 2 months of the HFD regimen, HFD mice were given daily metformin through oral gavage. Body weights, glucose tolerance, and retinal light responses were monitored regularly. Fluorescein angiography (FA) was used to assess changes in retinal vasculature. Ocular tissues (retina, vitreous, and lens) were harvested and analyzed for molecular changes as determined by immunofluorescent staining, Western blot analysis, and cytokine profiling. Starting 1 month after the diet regimen, mice fed the HFD had mildly compromised retinal light responses as measured by electroretinography (ERG), which worsened over time compared to that in the control. In HFD mice treated with metformin, systemic glucose levels reverted back to normal, and their weight gain slowed. Metformin reversed HFD-induced changes in phosphorylated protein kinase B (pAKT), extracellular signal-regulated kinase (pERK), and 5′AMP-activated protein kinase (pAMPK) in the retina. However, metformin treatments for 3 months did not restore the retinal light responses nor lessen the HFD-induced retinal neovascularization, even though it did reduce intraocular inflammation. Although metformin was able to reverse systemic changes induced by HFD, it was not able to restore HFD-caused retinal light responses or deter neovascularization.