Fuchs Endothelial Corneal Dystrophy and Mitochondria
Fuchs Endothelial Corneal Dystrophy and Mitochondria
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DOI：
10.1097/ico.0000000000001746
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发表时间：
2018-11-01
期刊：
影响因子：
2.8
通讯作者：
Miyai, Takashi
中科院分区：
文献类型：
--
作者：
Miyai, Takashi
Fuchs内皮性角膜营养不良（FECD）是一种双侧进行性角膜内皮疾病，其特征为肠瘘，表现为部分Descemet膜增厚，在终末期诱导角膜水肿。据报道，氧化应激在FECD的发病机制中起重要作用。线粒体中的电子传递链和氧化磷酸化（oxphos）系统是内源性氧化应激的主要来源，是由于过早的电子泄漏到氧气中产生超氧化物而引起的。在FECD中，角膜内皮细胞线粒体发生改变，线粒体DNA损伤，氧化蛋白减少，线粒体膜电位降低。线粒体动力学和线粒体自噬包括细胞器水平的线粒体质量控制系统。线粒体动力学包括融合和裂变过程。当线粒体严重受损时，分裂成为清除受损线粒体的主要过程。线粒体自噬是一种去除受损线粒体的选择性自噬途径，由线粒体膜电位去极化触发。在FECD角膜内皮中，线粒体具有分裂优势形态和低密度，因为线粒体改变的质量控制过程通过线粒体自噬上调。
Fuchs endothelial corneal dystrophy (FECD) is a bilateral progressive corneal endothelial disease characterized by guttae, which present as partial Descemet membrane thickening, inducing corneal edema at the final stage. Oxidative stress has been reported to play an important role in the pathogenesis of FECD. The electron transport chain and oxidative phosphorylation (oxphos) system in mitochondria are the main sources of endogenous oxidative stress, arising from superoxide generation through premature electron leakage to oxygen. In FECD, corneal endothelial cells have altered mitochondria with mitochondrial DNA damage, decreased oxphos proteins, and lower mitochondrial membrane potential. Mitochondrial dynamics and mitophagy comprise the organelle-level mitochondrial quality control system. Mitochondrial dynamics includes fusion and fission processes. When mitochondria are severely damaged, fission becomes the dominant process to remove damaged mitochondria. Mitophagy is a selective autophagy pathway that removes damaged mitochondria, and is triggered by mitochondrial membrane potential depolarization. In the FECD corneal endothelium, mitochondria have a fission-dominant morphology and low density through mitophagy upregulation because of quality control processes against altered mitochondria.