Age-related retinal inflammation is reduced by 670 nm light via increased mitochondrial membrane potential

Age-related retinal inflammation is reduced by 670 nm light via increased mitochondrial membrane potential
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DOI:
10.1016/j.neurobiolaging.2012.04.014
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发表时间:
2013-02-01
影响因子:
4.2
通讯作者:
Jeffery, Glen
Jeffery, Glen
中科院分区:
医学2区
文献类型:
--
作者:
Kokkinopoulos, Ioannis;Colman, Alan;Jeffery, Glen

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线粒体衰老理论认为,由线粒体 DNA 突变引起的氧化应激与三磷酸腺苷 (ATP) 产生减少导致细胞退化有关。这种退化的速度与代谢需求有关,其中外层视网膜在体内的代谢需求最大,表现出进行性炎症、巨噬细胞入侵和细胞损失,导致视力下降。 670 nm 光照射后,线粒体功能在体外发生变化,减少氧化应激并增加 ATP 产生。在体内,它改善诱发的病理。在这里,我们询问 670 nm 光是否会改变线粒体功能并减少与年龄相关的视网膜炎症。老年小鼠在 35 小时内仅接受 5 次每次 90 秒的照射。这显着增加了线粒体膜极化,并显着减少了巨噬细胞数量和肿瘤坏死因子(TNF)-α水平,这是一种关键的促炎细胞因子。评估了另外三种炎症标志物;补体成分 3d (C3d)、慢性炎症标志物和降钙素以及全身炎症生物标志物显着减少。补体成分 3b (C3b)(急性炎症标志物)没有显着改变。这些结果提供了一种在视觉功能下降的老龄化人群中对抗炎症的简单途径,并且可能适用于以视网膜炎症为关键特征的临床病症。 (C) 2013 Elsevier Inc. 保留所有权利。
The mitochondrial theory of aging argues that oxidative stress, caused by mitochondrial DNA mutations, is associated with decreased adenosine triphosphate (ATP) production leading to cellular degeneration. The rate of this degradation is linked to metabolic demand, with the outer retina having the greatest in the body, showing progressive inflammation, macrophage invasion, and cell loss, resulting in visual decline. Mitochondrial function shifts in vitro after 670-nm light exposure, reducing oxidative stress and increasing ATP production. In vivo, it ameliorates induced pathology. Here, we ask whether 670 nm light shifts mitochondrial function and reduces age-related retinal inflammation. Aged mice were exposed to only five 90-second exposures over 35 hours. This significantly increased mitochondrial membrane polarization and significantly reduced macrophage numbers and tumor necrosis factor (TNF)-alpha levels, a key proinflammatory cytokine. Three additional inflammatory markers were assessed; complement component 3d (C3d), a marker of chronic inflammation and calcitonin, and a systemic inflammatory biomarker were significantly reduced. Complement component 3b (C3b), a marker of acute inflammation, was not significantly altered. These results provide a simple route to combating inflammation in an aging population with declining visual function and may be applicable to clinical conditions where retinal inflammation is a key feature. (C) 2013 Elsevier Inc. All rights reserved.