Circadian rhythm disruption results in visual dysfunction.

Circadian rhythm disruption results in visual dysfunction.
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DOI:
10.1096/fba.2021-00125
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发表时间:
2022-06
期刊:
影响因子:
2.7
通讯作者:
--
中科院分区:
其他
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在过去的70年里,人造光的使用越来越多。反常的光暴露和工作的全天候性质导致了生物钟的破坏。昼夜节律紊乱(CRD)可导致多种代谢性和神经退行性疾病。然而,它对视力的影响尚不清楚。此外,哺乳动物的视网膜拥有一个自主时钟,可以在光照下重新设置。我们评估了CRD对视网膜形态、生理和视力的影响,将小鼠安置在诱导更短的明/暗周期(L10:D10)的干扰中。有趣的是,L10:D10下的小鼠表现出三种不同的夹带行为:“夹带”、“自由奔跑”和“之字形”。在CRD下的这些行为组表现出视力下降,视网膜变薄,以及光感受器数量减少。有趣的是,只有表现出“牵引性”行为的小鼠的视网膜电信号反应才会降低。视网膜蛋白质组在不同的夹带行为下表现出不同的变化,并且存在氧化应激-抗氧化机制的失调。这些结果表明,CRD改变了小鼠的缠绕行为,并导致了视觉功能障碍。我们的研究独一无二地显示了缠绕行为对视网膜生理的影响。我们的数据对理解和减轻CRD对视力的影响以及它在视网膜疾病病因学中的潜在作用具有更广泛的意义。
Artificial light has been increasingly in use for the past 70 years. The aberrant light exposure and round‐the‐clock nature of work lead to the disruption of biological clock. Circadian rhythm disruption (CRD) contributes to multiple metabolic and neurodegenerative diseases. However, its effect on vision is not understood. Moreover, the mammalian retina possesses an autonomous clock that could be reset with light exposure. We evaluated the impact of CRD on retinal morphology, physiology, and vision after housing mice in a disruption inducing shorter light/dark cycle (L10:D10). Interestingly, the mice under L10:D10 exhibited three different entrainment behaviors; “entrained,” “free‐running,” and “zigzagging.” These behavior groups under CRD exhibited reduced visual acuity, retinal thinning, and a decrease in the number of photoreceptors. Intriguingly, the electroretinogram response was decreased only in the mice exhibiting “entrained” behavior. The retinal proteome showed distinct changes with each entrainment behavior, and there was a dysfunctional oxidative stress‐antioxidant mechanism. These results demonstrate that CRD alters entrainment behavior and leads to visual dysfunction in mice. Our studies uniquely show the effect of entrainment behavior on retinal physiology. Our data have broader implications in understanding and mitigating the impact of CRD on vision and its potential role in the etiology of retinal diseases.