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非新生血管性AMD氧化应激和炎症对RPE的退行性改变影响

Datta, S., Cano, M., Ebrahimi, K., Wang, L., Handa, J.T.

期刊名称:Progress in Retinal and Eye Research

卷期:2017年第60卷

摘要

摘要:视网膜色素上皮(RPE)是一种高度特意化,独特的上皮细胞,在其顶端与感光细胞相互作用,并在其基底侧与Bruch膜和脉络膜毛细管相互作用。由于其具有保持光感受器健康的重要功能,RPE对于维持视力至关重要。随着老化和环境压力的积累,RPE可能出现功能失调,死亡。这种变性在年龄相关性黄斑变性(AMD)病理生物学中起着核心作用,这是西方社会老年人失明的主要原因。氧化应激和炎症在RPE变性中具有生理学和潜在的病理作用。鉴于RPE的核心作用,本综述将侧重于氧化应激和炎症对具有AMD病理生物学的RPE的影响。将讨论氧化应激的生理来源以及光氧化应激的独特来源,光感受器外段的吞噬作用,以及可将氧化应激转化为病理作用的可改变因素如吸烟和高脂肪饮食摄入,以及线粒体动力学和Nrf2信号系统对AMDRPE健康的保护作用受损的负面影响。同样,还将讨论先天性免疫系统对刺激性触发的反应,以及局部RPE发生炎症的潜在作用,以及如果刺激性触发不被中和,炎症与慢性损伤的潜在作用。

The retinal pigment epithelium (RPE) is a highly specialized, unique epithelial cell that interacts with photoreceptors on its apical side and with Bruch's membrane and the choriocapillaris on its basal side. Due to vital functions that keep photoreceptors healthy, the RPE is essential for maintaining vision. With aging and the accumulated effects of environmental stresses, the RPE can become dysfunctional and die. This degeneration plays a central role in age-related macular degeneration (AMD) pathobiology, the leading cause of blindness among the elderly in western societies. Oxidative stress and inflammation have both physiological and potentially pathological roles in RPE degeneration. Given the central role of the RPE, this review will focus on the impact of oxidative stress and inflammation on the RPE with AMD pathobiology. Physiological sources of oxidative stress as well as unique sources from photo-oxidative stress, the phagocytosis of photoreceptor outer segments, and modifiable factors such as cigarette smoking and high fat diet ingestion that can convert oxidative stress into a pathological role, and the negative impact of impairing the cytoprotective roles of mitochondrial dynamics and the Nrf2 signaling system on RPE health in AMD will be discussed. Likewise, the response by the innate immune system to an inciting trigger, and the potential role of local RPE production of inflammation, as well as a potential role for damage by inflammation with chronicity if the inciting trigger is not neutralized, will be debated.


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