Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration
Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration
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DOI：
10.1016/j.neurobiolaging.2005.05.012
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发表时间：
2006-07-01
影响因子：
4.2
通讯作者：
Gabrieli, Corrado Balacco
中科院分区：
文献类型：
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作者：
Feher, Janos;Kovacs, Illes;Gabrieli, Corrado Balacco
线粒体功能障碍与几种年龄相关疾病的病理生理学有关，包括年龄相关性黄斑变性（AMD），一种主要影响视网膜色素上皮（RPE）的进行性神经变性疾病。我们的电子显微镜和形态学研究的目的是揭示定性和定量的线粒体在人类视网膜色素上皮的AMD和年龄和性别匹配的控制。随着年龄的增长，AMD和对照组的线粒体数量和面积显着减少，以及嵴和基质密度的损失。这些减少在AMD中比在正常老化中显著更大。线粒体的改变伴随着增殖的过氧化物酶体和脂褐质颗粒在AMD和对照标本，虽然组间的差异是显着的过氧化物酶体。出乎意料的是，形态测量数据显示，在AMD中观察到的RPE改变也可能在正常衰老中发展，在AMD患者中出现后10-15年。这些发现表明：（i）AMD和正常衰老之间线粒体和过氧化物酶体改变的严重程度不同，以及（ii）RPE损伤的时间可能对AMD的发展至关重要。我们的结论是，除了线粒体DNA的年龄相关的变化，线粒体膜的改变也可能在AMD的发病机制中发挥作用。这些膜可能成为治疗AMD和其他年龄相关疾病的新靶点。(c)2005年爱思唯尔公司All rights reserved.
Mitochondrial dysfunctions have been implicated in the pathophysiology of several age-related diseases including age-related macular degeneration (AMD), a progressive neurodegenerative disease affecting primarily the retinal pigment epithelium (RPE). The aims of our electron microscopic and morphometric studies were to reveal qualitative and quantitative alterations of mitochondria in human RPE from AMD and from age- and sex-matched controls. With increasing age a significant decrease in number and area of mitochondria, as well as loss of cristae and matrix density were found in both AMD and control specimens. These decreases were significantly greater in AMD than in normal aging. Alterations of mitochondria were accompanied by proliferation of peroxisomes and lipofuscin granules in both AMD and control specimens, although the difference between groups was significant only for peroxisomes. Unexpectedly, morphometric data showed that the RPE alterations seen in AMD may also develop in normal aging, 10-15 years after appearing in AMD patients. These findings suggest that (i) the severity of mitochondrial and peroxisomal alterations are different between AMD and normal aging, and (ii) the timing of damage to RPE may be critical for the development of AMD. We conclude that besides the well-documented age-related changes in mitochondrial DNA, alterations of mitochondrial membranes may also play a role in the pathogenesis of AMD. These membranes could be a new target for treatment of AMD and other age-related diseases. (c) 2005 Elsevier Inc. All rights reserved.