Elsevier

Redox Biology

Volume 30, February 2020, 101417
Redox Biology

Research Paper
Peroxiredoxin-1 regulates lipid peroxidation in corneal endothelial cells

https://doi.org/10.1016/j.redox.2019.101417Get rights and content
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Highlights

  • PRDX1 is a key regulator of lipid peroxidation.

  • Expression of PRDX1 is lost in Fuchs' endothelial corneal dystrophy.

  • Oxidative stress reduces PRDX1 expression in cultures of CEnCs.

Abstract

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.

Keywords

PRDX1
Corneal endothelial cells
Fuchs' endothelial corneal dystrophy
Lipid peroxidation
Ferroptosis

Abbreviations

AnV
Annexin V
ARE
antioxidant response element
CEnC
Corneal Endothelial cell
CH
cumene hydroperoxide
DM
Descemet's membrane
FECD
Fuchs' endothelial corneal dystrophy
Fer-1
ferrostatin-1
GPX4
Glutathione peroxidase 4
GSH
Glutathione
NRF2
nuclear factor-like 2
PI
Propidium iodide
PRDX
peroxiredoxin
ROS
reactive oxygen species

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