D’Ercole, Joseph-Oxidative Stress in Fuchs’ Dystrophy: Changes in Metabolism, Transcriptional Activity, and the Extracellular Matrix (Dr. Michelle MacDonald)

Oxidative Stress in Fuchs’ Dystrophy: Changes in Metabolism, Transcriptional Activity, and the Extracellular Matrix

Fuchs Endothelial Corneal Dystrophy (FECD) is among the most common corneal diseases affecting the endothelial cell layer of the human cornea. FECD manifests as progressive cell death as well as depositions of the extracellular matrix (ECM) known as guttae. As endothelial cells continue to die,  the tissue’s function may be compromised and lead to corneal edema. Furthermore,  guttae cause light to scatter,  creating visual disturbances. Both corneal edema and guttae lead to a decrease in vision and,  in severe cases,  an effective total loss of vision. Currently,  treatments may only temporarily alleviate corneal edema,  and transplantation is the only effective solution. As such,  there is an apparent need to better understand and treat FECD. Though the cause of FECD currently remains unknown,  previous research has characterized numerous aspects of this disease. This review article will summarize and analyze the current state of the literature by focusing on three components of FECD: 1) metabolic changes,  2) transcriptional and proteomic alterations and,  3) excessive ECM synthesis. The pathogenesis will also be considered,  as oxidative stress,  likely from mitochondrial metabolism,  has been documented and implicated as a risk factor for developing FECD and may explain some observed biochemical changes. As the current body of knowledge on FECD is incomplete,  various experimental protocols are also proposed in relation to the aforementioned components. These protocols will serve to better investigate previously characterized aspects of FECD,  while also probing into unstudied facets to drive further research and lead to a more holistic understanding of FECD.,