Abstract
Purpose :
The exact aetiology of the Fuchs endothelial corneal dystrophy (FECD) is not well determined but evidence accumulates about the implication of oxidative stress and mitochondrial dysfunction as contributing factors. Previous work in our lab has shown that corneal endothelial cells from FECD patients have shorter telomeres and increased mitochondrial levels, indicators of oxidative stress. We have also shown that each individual cell in FECD is not equally affected and that different cells are presenting different mitochondrial levels. We hypothesised that FECD cells enter a vicious cycle in which oxidative stress causes mitochondrial dysfunction and leads to cell death. When cells die, the energy required from each remaining cell to achieve the corneal endothelial function is increased. This leads to a mitochondrial activity increase, oxidative stress and ultimately to cell death, feeding the vicious cycle. The objective of the project was to determine the mitochondrial exhaustion status in FECD in order to evaluate the progression of the pathology.
Methods :
Different biomarkers have been used on corneal endothelium explants from healthy and FECD patients to measure oxidative stress, apoptosis and mitochondrial calcium level and membrane potential. Mitotracker staining has been used to correlate the measured biomarkers with mitochondrial mass level.
Results :
Using the different biomarkers, we have determined a sequence of events in FECD progression in which mitochondria are central. The mitochondrial mass enabled us to distinguish different populations of cells with different characteristics within the same explant. This suggests that each endothelial cell is not at the same progression stage of the pathology.
Conclusions :
Taken together, our results indicate that a depletion of cellular density in corneal endothelium forces mitochondria of the remaining cells to work to exhaustion in order to maintain the function of the corneal endothelium. This generates oxidative stress and eventually leads to a mitochondrial «burnout» causing the death of endothelial cells. This cellular death feeds the cycle of cellular depletion central to the pathology.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.