Treatment with 670 nm light up regulates cytochrome C oxidase expression and reduces inflammation in an age-related macular degeneration model.
Treatment with 670 nm light up regulates cytochrome C oxidase expression and reduces inflammation in an age-related macular degeneration model.
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DOI：
10.1371/journal.pone.0057828
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jeffery G
中科院分区：
文献类型：
--
作者：
Begum R;Powner MB;Hudson N;Hogg C;Jeffery G
炎症是衰老的一个总括特征。它存在于老年视网膜和许多视网膜疾病，包括年龄相关性黄斑变性（AMD）。在衰老和AMD中，线粒体功能下降。在正常衰老过程中，这可以通过在视网膜上短暂暴露于670 nm光来操纵，这会增加线粒体膜电位并减少炎症。在这里，我们询问670 nm曝光是否在老年AMD小鼠模型中具有相同的能力，补体因子H敲除（CFH-/-），其中炎症是一个关键特征。此外，我们问当670 nm在环境照明中短暂传递而不是直接聚焦在视网膜上时是否会发生这种情况。将小鼠以补充环境光的形式暴露于670 nm，每天两次，每次6分钟，持续14天。暴露动物的细胞色素c氧化酶（考克斯，这是一种线粒体酶调节氧化磷酸化）显著增加，补体成分C3（视网膜外层的炎症标记物）显著减少。Vimetin和胶质细胞酸性蛋白（GFAP）的表达，反映视网膜应力在穆勒神经胶质细胞，也显着下调。外视网膜巨噬细胞形态也有显著变化。然而，淀粉样蛋白β（Aβ）负荷，也随着年龄的增长而增加，在视网膜外层，是促炎性的，没有改变。因此，即使通过环境照明进行短暂暴露，670 nm也能有效减少基因型与50% AMD患者相似的小鼠的炎症，可能是通过考克斯激活来实现的。此外，炎症可以独立于Aβ而减少。这里揭示的疗效支持目前在AMD患者中进行的670 nm的早期临床试验。
Inflammation is an umbrella feature of ageing. It is present in the aged retina and many retinal diseases including age-related macular degeneration (AMD). In ageing and in AMD mitochondrial function declines. In normal ageing this can be manipulated by brief exposure to 670 nm light on the retina, which increases mitochondrial membrane potential and reduces inflammation. Here we ask if 670 nm exposure has the same ability in an aged mouse model of AMD, the complement factor H knockout (CFH−/−) where inflammation is a key feature. Further, we ask whether this occurs when 670 nm is delivered briefly in environmental lighting rather than directly focussed on the retina. Mice were exposed to 670 nm for 6 minutes twice a day for 14 days in the form of supplemented environmental light. Exposed animals had significant increase in cytochrome c oxidase (COX), which is a mitochondrial enzyme regulating oxidative phosphorylation.There was a significant reduction in complement component C3, an inflammatory marker in the outer retina. Vimetin and glial fibrillary acidic protein (GFAP) expression, which reflect retinal stress in Muller glia, were also significantly down regulated. There were also significant changes in outer retinal macrophage morphology. However, amyloid beta (Aβ) load, which also increases with age in the outer retina and is pro-inflammatory, did not change. Hence, 670 nm is effective in reducing inflammation probably via COX activation in mice with a genotype similar to that in 50% of AMD patients even when brief exposures are delivered via environmental lighting. Further, inflammation can be reduced independent of Aβ. The efficacy revealed here supports current early stage clinical trials of 670 nm in AMD patients.
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