Neuroprotective effect of activated 5'-adenosine monophosphate-activated protein kinase on cone system function during retinal inflammation.
Neuroprotective effect of activated 5'-adenosine monophosphate-activated protein kinase on cone system function during retinal inflammation.
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DOI：
10.1186/s12868-016-0268-5
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发表时间：
2016-06-10
期刊：
影响因子：
2.4
通讯作者：
Ozawa Y
中科院分区：
文献类型：
--
作者：
Kamoshita M;Fujinami K;Toda E;Tsubota K;Ozawa Y
视网膜炎症可引起视网膜神经紊乱。特别是，视锥光感受器系统中的功能障碍影响视敏度。然而，其基本机制尚未完全了解。在这项研究中，我们评估视锥细胞系统的功能和5′-腺苷一磷酸激活的蛋白激酶（AMPK）在视网膜炎症过程中的作用。六至八周龄的雄性C57 BL/6小鼠接受脂多糖（LPS）的腹膜内注射以诱导视网膜炎症，并且在LPS注射前3小时用AMPK激活剂、5-氨基咪唑-4-甲酰胺核糖核苷（AICAR; 250 mg/kg体重）或磷酸盐缓冲盐水作为媒介物处理。代表视锥系统功能的明视视网膜电图的b波在LPS注射后24小时降低，并且这种降低被AICAR治疗抑制。在该时间点，视锥光感受器细胞中没有显著的形态学变化。在LPS注射后1.5 h，视网膜炎性细胞因子TNF-α的mRNA水平升高，线粒体生物合成调节因子Pgc 1-α的mRNA水平降低。然而，AICAR治疗抑制这些mRNA表达的变化。免疫组化结果显示，注射LPS后24 h，AICAR也抑制了胶质细胞酸性蛋白的表达。此外，用AICAR处理小鼠视锥光感受器衍生的细胞系661 W以增加磷酸化和活化的AMPK的水平。AICAR作用3 h后，661 W细胞TNF-α mRNA水平下降，Pgc 1-α mRNA水平升高。AMPK活化对炎症期间的视锥系统功能具有神经保护作用，并且该作用可能至少部分涉及炎症细胞因子和线粒体状况的调节。
Retinal inflammation can cause retinal neural disorders. In particular, functional disorder in the cone photoreceptor system influences visual acuity. However, the underlying mechanism is not yet fully understood. In this study, we evaluated cone system function and the role of 5′-adenosine monophosphate-activated protein kinase (AMPK) during retinal inflammation. Six to eight-week-old male C57BL/6 mice received an intraperitoneal injection of lipopolysaccharide (LPS) to induce retinal inflammation, and were treated with an AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR; 250 mg/kg body weight) or phosphate-buffered saline as vehicle 3 h before the LPS injection. The b-wave of the photopic electroretinogram, which represents cone system function, was decreased 24 h after LPS injection and this reduction was suppressed by AICAR treatment. At this time point, there was no remarkable morphological change in the cone photoreceptor cells. At 1.5 h after LPS injection, the retina mRNA levels of an inflammatory cytokine, Tnf-α, were increased, and those of a regulator of mitochondrial biogenesis, Pgc1-α, were decreased. However, AICAR treatment suppressed these changes in mRNA expression. Immunohistochemistry showed that induction of glial fibrillary acidic protein expression was also suppressed by AICAR 24 h after LPS injection. Furthermore, the mouse cone photoreceptor-derived cell line 661W was treated with AICAR to increase the level of phosphorylated and activated AMPK. After 3 h of AICAR incubation, 661W cells showed decreased Tnf-α mRNA levels and increased Pgc1-α mRNA levels. AMPK activation has a neuroprotective effect on cone system function during inflammation, and the effect may, at least in part, involve the regulation of inflammatory cytokines and mitochondrial condition.