Lovatt Matthew, Adnan Khadijah, Peh Gary S L, Mehta Jodhbir S
Tissue Engineering and Stem Cell group, Singapore Eye Research Institute (SERI), Singapore 169856, Singapore.
Eye-ACP, Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
Antioxidants (Basel). 2018 Dec 4;7(12):180. doi: 10.3390/antiox7120180.
The inner layer of the cornea, the corneal endothelium, is post-mitotic and unable to regenerate if damaged. The corneal endothelium is one of the most transplanted tissues in the body. Fuchs' endothelial corneal dystrophy (FECD) is the leading indication for corneal endothelial transplantation. FECD is thought to be an age-dependent disorder, with a major component related to oxidative stress. Prdx6 is an antioxidant with particular affinity for repairing peroxidised cell membranes. To address the role of Prdx6 in corneal endothelial cells, we used a combination of biochemical and functional studies. Our data reveal that Prdx6 is expressed at unusually high levels at the plasma membrane of corneal endothelial cells. RNAi-mediated knockdown of Prdx6 revealed a role for Prdx6 in lipid peroxidation. Furthermore, following induction of oxidative stress with menadione, Prdx6-deficient cells had defective mitochondrial membrane potential and were more sensitive to cell death. These data reveal that Prdx6 is compartmentalised in corneal endothelial cells and has multiple functions to preserve cellular integrity.
角膜的内层，即角膜内皮，是有丝分裂后细胞，受损后无法再生。角膜内皮是人体中移植最多的组织之一。富克斯内皮性角膜营养不良（FECD）是角膜内皮移植的主要适应症。FECD被认为是一种年龄依赖性疾病，其主要成分与氧化应激有关。Prdx6是一种抗氧化剂，对修复过氧化细胞膜具有特殊亲和力。为了研究Prdx6在角膜内皮细胞中的作用，我们结合了生化和功能研究。我们的数据显示，Prdx6在角膜内皮细胞质膜上以异常高的水平表达。RNAi介导的Prdx6敲低揭示了Prdx6在脂质过氧化中的作用。此外，在用甲萘醌诱导氧化应激后，缺乏Prdx6的细胞线粒体膜电位存在缺陷，对细胞死亡更敏感。这些数据表明，Prdx6在角膜内皮细胞中是分隔存在的，并且具有多种功能来维持细胞完整性。
