Autophagy in the retina: a potential role in age-related macular degeneration.

Autophagy in the retina: a potential role in age-related macular degeneration.
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DOI:
10.1007/978-1-4614-0631-0_12
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发表时间:
2012
影响因子:
--
通讯作者:
Boulton, Michael E.
Boulton, Michael E.
中科院分区:
医学4区
文献类型:
--
作者:
Mitter, Sayak K.;Rao, Haripriya Vittal;Qi, Xiaoping;Cai, Jun;Sugrue, Andrew;Dunn, William A., Jr.;Grant, Maria B.;Boulton, Michael E.

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年龄相关性黄斑变性 (AMD) 与多种遗传和细胞缺陷有关,这些缺陷导致共同的终点:视网膜变性。衰老和氧化应激是 AMD 发病机制的重要特征,与一系列年龄相关疾病和神经退行性疾病中细胞内细胞器受损和自噬通量缺陷的增加有关。自噬是维持细胞稳态的关键过程,可去除功能失调的细胞器和蛋白质。自噬蛋白在视网膜中强烈表达,现在有强有力的证据表明线粒体损伤和自噬缺陷是视网膜老化的一个特征,并且这种情况在 AMD 中进一步加剧。很明显,自噬对 RPE 中脂褐质的积累做出了重大贡献。自噬的药理学操作可能为 AMD 提供替代治疗靶点。
Age-related macular degeneration (AMD) is associated with multiple genetic and cellular defects which lead to a common endpoint, retinal degeneration. Aging and oxidative stress, significant features in the pathogenesis of AMD, are associated with an increase in damaged intracellular organelles and defective autophagy flux in a range of age-related and neurodegenerative diseases. Autophagy is a key process in maintenance of cellular homeostasis that serves to remove dysfunctional organelles and proteins. Autophagy proteins are strongly expressed in the retina and there is now strong evidence that mitochondrial damage and defective autophagy are a feature of the aging retina and that this is further exacerbated in AMD. It is apparent that autophagy makes a significant contribution to lipofuscin accumulation in the RPE. Pharmacological manipulation of autophagy may offer an alternative therapeutic target in AMD.
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