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Matt Lovatt, Viridiana Kocaba, Jodhbir S Mehta; Regulation of lipid peroxidation in corneal endothelial cells by peroxiredoxin 1.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2151.
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© ARVO (1962-2015); The Authors (2016-present)
The peroxiredoxin (Prdx) family of redox sensors have been implicated in the pathogenesis of Fuchs Corneal Endothelial Dystrophy (FECD). However, the molecular mechanism regarding their function in corneal endothelial cells has not been explored.
We performed biochemical analysis of Prdx expression in corneal endothelial cells from control and FECD patient samples. We used RNAi to knockdown Prdx expression in corneal endothelial cells and, functional assays to determine the role of individual Prdx family members in corneal endothelial cells. We measured the response of corneal endothelial cells to inducers of oxidative stress including, menadione, tert butyl hydroperoxide and cumene hydroperoxide. Apoptosis, lipid peroxidation, mitochondrial membrane potential and cell viability assays were performed using flow cytometry and xCELLigence real time cell analysis.
We reveal for the first time that Prdx1 expression is lost in corneal endothelial cells undergoing oxidative stress. Importantly we reveal the specific downregulation of Prdx1 in FECD tissue. We uncover a novel role for Prdx1 in regulating lipid peroxidation induced by cumene hydroperoxide in corneal endothelial cells. Importantly, we demonstrate that Prdx1 controls cell death thorough non-apoptotic pathways reminiscent of ferroptosis. Interestingly, inhibitors of ferroptosis restore Prdx1 expression and cell viability in corneal endothelial cells
Targeting the Prdx1/ferroptosis pathway could lead to a novel strategy for treatment of FECD.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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