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锌与年龄相关性黄斑变性中的自噬作用。

Zinc and Autophagy in Age-Related Macular Degeneration.

机构信息

Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.

Department of Orthodontics, Medical University of Lodz, 92-216 Lodz, Poland.

出版信息

Int J Mol Sci. 2020 Jul 15;21(14):4994. doi: 10.3390/ijms21144994.

Abstract

Zinc supplementation is reported to slow down the progression of age-related macular degeneration (AMD), but there is no general consensus on the beneficiary effect on zinc in AMD. As zinc can stimulate autophagy that is declined in AMD, it is rational to assume that it can slow down its progression. As melanosomes are the main reservoir of zinc in the retina, zinc may decrease the number of lipofuscin granules that are substrates for autophagy. The triad zinc-autophagy-AMD could explain some controversies associated with population studies on zinc supplementation in AMD as the effect of zinc on AMD may be modulated by genetic background. This aspect was not determined in many studies regarding zinc in AMD. Zinc deficiency induces several events associated with AMD pathogenesis, including increased oxidative stress, lipid peroxidation and the resulting lipofuscinogenesis. The latter requires autophagy, which is impaired. This is a vicious cycle-like reaction that may contribute to AMD progression. Promising results with zinc deficiency and supplementation in AMD patients and animal models, as well as emerging evidence of the importance of autophagy in AMD, are the rationale for future research on the role of autophagy in the role of zinc supplementation in AMD.

摘要

锌补充据称可减缓与年龄相关的黄斑变性(AMD)的进展,但对于 AMD 中锌的受益效果尚无普遍共识。由于锌可以刺激在 AMD 中下降的自噬,因此可以合理地假设它可以减缓其进展。由于黑色素体是视网膜中锌的主要储存库,因此锌可能会减少自噬的底物脂褐素颗粒的数量。锌-自噬-AMD 三联体可以解释与 AMD 中锌补充的人群研究相关的一些争议,因为锌对 AMD 的作用可能受遗传背景的调节。在许多关于 AMD 中锌的研究中,尚未确定这一方面。锌缺乏会引起与 AMD 发病机制相关的几种事件,包括氧化应激增加、脂质过氧化和由此产生的脂褐素生成。后者需要自噬,而自噬受损。这是一种可能导致 AMD 进展的类似恶性循环的反应。锌缺乏和补充在 AMD 患者和动物模型中的有希望的结果,以及自噬在 AMD 中的重要性的新证据,为锌补充在 AMD 中的作用的自噬作用的未来研究提供了依据。

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