Restoration of mitochondrial integrity, telomere length, and sensitivity to oxidation by in vitro culture of Fuchs’ endothelial corneal dystrophy cells
Article [Version publiée]
Fait partie de
Investigative ophthalmology and visual science ; vol. 57, p. 5926-5934.Éditeur·s
Association for research in vision and ophthalmologyAuteur·e·s
Résumé·s
PURPOSE. Fuchs’ endothelial corneal dystrophy (FECD), a degenerative disease of the corneal
endothelium that leads to vision loss, is a leading cause of corneal transplantation. The cause
of this disease is still unknown, but the implication of oxidative stress is strongly suggested. In
this study, we analyzed the impact of FECD on mitochondrial DNA (mtDNA) integrity and
telomere length, both of which are affected by the oxidative status of the cell.
METHODS. We compared the levels of total mtDNA, mtDNA common deletion (4977 bp), and
relative telomere length in the corneal endothelial cells of fresh Descemet’s membraneendothelium explants and cultured cells from healthy and late stage FECD subjects. Oxidantantioxidant gene expression and sensitivity to ultraviolet A (UVA)- and H2O2-induced cell
death were assessed in cultured cells.
RESULTS. Our results revealed increased mtDNA levels and telomere shortening in FECD
explants. We also found that cell culture restores a normal phenotype in terms of mtDNA
levels, telomere length, oxidant-antioxidant gene expression balance, and sensitivity to
oxidative stress-induced cell death in the FECD cells compared with the healthy cells.
CONCLUSIONS. Taken together, these results bring new evidence of the implication of oxidative
stress in FECD. They also show that FECD does not evenly affect the integrity of corneal
endothelial cells and that cell culture can rehabilitate the molecular phenotypes related to
oxidative stress by selecting the more functional FECD cells.