A study, led by joint team of researchers from Université Laval and Université Montréal and recently published in Scientific Reports, measured the efficacy of a new treatment for Fuchs’ endothelial corneal dystrophy (FECD) that rehabilitates damaged mitochondria.
Give me some background.
Earlier research from the same team showed that due to the accelerated loss of endothelial cells associated with FECD, the mitochondria of surviving endothelial cells must produce more energy to compensate, inducing mitochondrial burnout.
This process leads to cell death and sets into motion a deleterious cycle of FECD progression that can cause corneal edema and, eventually, irreversible vision loss.
Now talk about this study.
Researchers assessed if incorporating healthy exogenous mitochondria into late-stage FECD-affected endothelial cells would improve pathological molecular markers of the disease.
To internalize the exogenous mitochondria in the FECD-affected cells, investigators incubated corneal endothelial explants from patients with FECD with isolated mitochondria from cultured cells.
Findings?
Investigators found that the internalization of healthy mitochondria in FECD cells reduced levels of oxidative stress and increased mitochondrial membrane potential (a key indicator of mitochondrial activity), as well as reduced mitophagy.
Additionally, reduced levels of apoptosis (57% in FECD cells vs. 12% in FECD cells with internalized mitochondria) were observed.
Tell me more.
The incorporation of healthy mitochondria caused an increase in mitochondrial membrane potential as soon as 3 hours after exposure. Further, after 48 hours, the mitochondrial membrane potential continued to rise.
This is likely due to the improved removal of damaged mitochondria via mitophagy from the introduction of the fully functional mitochondria.
Significance?
Currently, the only curative treatment for FECD is corneal transplantation, an invasive procedure that can be delayed as patients wait for viable grafts.
However this study shows that mitochondrial transplantation rehabilitates and reverses the cycle of mitochondrial burnout and cell death, potentially providing a novel therapy for FECD.
Further studies using in vivo models are required to more accurately measure the efficacy of this treatment.