Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE.
Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE.
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DOI：
10.1167/iovs.18-24289
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发表时间：
2018-03-20
影响因子：
4.4
通讯作者：
Ferrington DA
中科院分区：
文献类型：
--
作者：
Fisher CR;Ferrington DA
黄斑变性是发达国家致盲的主要原因。干型AMD，也称为萎缩性AMD，其特征是RPE和光感受器的死亡。目前，还没有治疗这种疾病的方法，部分原因是我们对引起AMD的机制了解不完全。来自人类供体AMD研究的有力实验证据支持RPE线粒体缺陷驱动AMD病理的新假设。这些研究使用了不同的实验方法，表明来自AMD供体的RPE原代培养物的RPE线粒体结构被破坏，线粒体数量和质量减少，多种线粒体蛋白含量改变，线粒体DNA损伤增加，与疾病严重程度相关，生物能量学缺陷。在这里，我们讨论了代谢解耦的模型，改变病变视网膜的生物能量学和驱动AMD病理。这些数据为靶向RPE中的线粒体作为最有效的干预策略提供了理论依据，如果在视力丧失和细胞死亡之前早期给予。
AMD is the leading cause of blindness in developed countries. The dry form of AMD, also known as atrophic AMD, is characterized by the death of RPE and photoreceptors. Currently, there are no treatments for this form of the disease due in part to our incomplete understanding of the mechanism causing AMD. Strong experimental evidence from studies of human donors with AMD supports the emerging hypothesis that defects in RPE mitochondria drive AMD pathology. These studies, using different experimental methods, have shown disrupted RPE mitochondrial architecture and decreased mitochondrial number and mass, altered content of multiple mitochondrial proteins, increased mitochondrial DNA damage that correlates with disease severity, and defects in bioenergetics for primary RPE cultures from AMD donors. Herein, we discuss a model of metabolic uncoupling that alters bioenergetics in the diseased retina and drives AMD pathology. These data provide the rationale for targeting the mitochondria in the RPE as the most efficacious intervention strategy if administered early, before vision loss and cell death.
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影响因子：
11.4
作者：
Ferrington DA;Ebeling MC;Kapphahn RJ;Terluk MR;Fisher CR;Polanco JR;Roehrich H;Leary MM;Geng Z;Dutton JR;Montezuma SR
通讯作者：
Montezuma SR
影响因子：
4.2
作者：
Feher, Janos;Kovacs, Illes;Gabrieli, Corrado Balacco
通讯作者：
Gabrieli, Corrado Balacco
DOI：
10.1073/pnas.222551899
发表时间：
2002-11-12
影响因子：
11.1
作者：
Crabb, JW;Miyagi, M;Hollyfield, JG
通讯作者：
Hollyfield, JG
DOI：
10.1016/j.bbagrm.2012.06.002
发表时间：
2012-09
影响因子：
4.7
作者：
Cline, Susan D.
通讯作者：
Cline, Susan D.
影响因子：
7.7
作者：
Feuermann, M;Francisci, S;Bolotin-Fukuhara, M
通讯作者：
Bolotin-Fukuhara, M