Mutagenesis of mitochondrial DNA in Fuchs endothelial corneal dystrophy
Mutagenesis of mitochondrial DNA in Fuchs endothelial corneal dystrophy
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DOI：
10.1016/j.mrfmmm.2013.12.001
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发表时间：
2014-02-01
影响因子：
2.3
通讯作者：
Szaflik, J. P.
中科院分区：
文献类型：
--
作者：
Czarny, P.;Seda, A.;Szaflik, J. P.
Fuchs角膜内皮营养不良（FECD）是一种与年龄相关的缓慢进展性疾病，可导致角膜内皮细胞凋亡、角膜后弹力层功能障碍和角膜水肿，导致视力丧失。越来越多的证据表明，氧化应激可能在FECD的发病机制中发挥重要作用，CE细胞的线粒体是其主要靶点。线粒体DNA（mtDNA）特别容易受到氧化应激的影响，并且在FECD患者中报告了mtDNA的变化。在本工作中，我们研究了线粒体DNA的损伤和修复，线粒体DNA拷贝数，和4977 bp的共同缺失的线粒体DNA在DM细胞和外周血淋巴细胞（PBL）分离FECD患者。来自35例FECD患者和32例对照的PBL用20 μ M的过氧化氢激发10 min，然后在新鲜培养基中放置3 h，导致两组mtDNA拷贝数减少。线粒体DNA的损伤在3小时后没有完全修复，患者的剩余病变程度明显高于对照组。我们观察到FECD患者DM细胞中的拷贝数更高，线粒体DNA损伤程度增加，常见4977 bp缺失的比例也高于对照组。我们的研究结果证实，线粒体DNA的突变可能参与FECD的发病机制和线粒体DNA对损伤剂的敏感性的障碍，以及线粒体DNA损伤修复的变化沿着线粒体DNA拷贝数的变化可能强调这种参与。(C)2013爱思唯尔有限公司版权所有。
Fuchs endothelial corneal dystrophy (FECD) is an age-related, slowly progressive disease, which may lead to loss of vision resulting from apoptosis of corneal endothelial (CE) cells, dysfunction of Descemet membrane (DM) and corneal edema. A growing body of evidence suggests that oxidative stress may play a major role in the pathogenesis of FECD and that mitochondria of CE cells are its main target. Mitochondrial DNA (mtDNA) is particularly prone to oxidative stress and changes in mtDNA were reported in FECD patients. In the present work we studied mtDNA damage and repair, mtDNA copy number, and the 4977 bp common deletion in mtDNA in DM cells and peripheral blood lymphocytes (PBLs) isolated from FECD patients. PBLs from 35 FECD patients and 32 controls were challenged for 10 min with hydrogen peroxide at 20 mu M and then left in a fresh medium for 3 h, resulting in a decrease in mtDNA copy number in both groups. Damage to mtDNA was not fully repaired after 3 h and the extent of remaining lesions was significantly higher in the patients than the controls. We observed a higher copy number and an increased extent of mtDNA damage as well as a higher ratio of the common 4977 bp deletion in DM cells of FECD patients than the controls. Our results confirm that mutagenesis of mtDNA may be involved in FECD pathogenesis and disturbance in mtDNA sensitivity to damaging agent as well as changes in mtDNA damage repair along with alternations in mtDNA copy number may underline this involvement. (C) 2013 Elsevier B.V. All rights reserved.