Corneal transparency is maintained by a monolayer of corneal endothelial cells. Defects in corneal endothelial cells (CEnCs) can be rectified surgically through transplantation. Fuchs’ endothelial corneal dystrophy (FECD) is the foremost cause of endothelial dysfunction and the leading indication for transplantation. Increased sensitivity of CEnCs to oxidative stress is thought to contribute to the pathogenesis of FECD through increased apoptosis. In part, this is thought to be due to loss of NRF2 expression: a global regulator of oxidative stress. We demonstrate that expression of the redox sensor, peroxiredoxin 1 (PRDX1) is selectively lost from CEnCs in FECD patient samples. We reveal that expression of PRDX1 is necessary to control the response of CEnCs to agents that cause lipid peroxidation. Iron-dependent lipid peroxidation drives non-apoptotic cell death termed ferroptosis. We establish that the inhibitor of ferroptosis, ferrostatin-1 rescues lipid peroxidation and cell death in CEnCs. Furthermore, we provide evidence that the transcription factor NRF2 similarly regulates lipid peroxidation in CEnCs.

通过单层角膜内皮细胞维持角膜透明性。角膜内皮细胞（CEnCs）的缺陷可以通过移植手术修复。Fuchs的内皮角膜营养不良（FECD）是引起内皮功能障碍的最主要原因，也是移植的主要指征。CEnCs对氧化应激的敏感性增加被认为通过增加细胞凋亡促进了FECD的发病。在某种程度上，这被认为是由于NRF2表达的丧失：一种氧化应激的整体调节剂。我们证明氧化还原传感器，peroxiredoxin 1（PRDX1）的表达选择性地从FECD患者样品中的CEnCs丢失。我们揭示PRDX1的表达是必要的，以控制CEnCs引起脂质过氧化反应的试剂的反应。铁依赖性脂质过氧化驱动非凋亡性细胞死亡，称为肥大病。我们建立了肥大病的抑制剂，ferrostatin-1可以拯救CEnCs中的脂质过氧化作用和细胞死亡。此外，我们提供证据，转录因子NRF2类似地调节CEnCs中的脂质过氧化。