Nrf2: A unifying transcription factor in the pathogenesis of Fuchs' endothelial corneal dystrophy

Abstract

Nuclear factor, erythroid 2 like 2 (Nrf2), is an oxidative stress induced transcription factor that regulates cytoprotective gene expression. Thus, Nrf2 is essential for cellular redox homeostasis. Loss or dysregulation of Nrf2 expression has been implicated in the pathogenesis of degenerative diseases, including diseases of the cornea. One of the most common diseases of the cornea in which Nrf2 is implicated is Fuchs' endothelial cornea dystrophy (FECD). FECD is the leading indication for corneal transplantation; and is associated with a loss of corneal endothelial cell (CEC) function. In this review, we propose that Nrf2 is an essential regulator of CEC function. Furthermore, we demonstrate that deficiency of Nrf2 function is a hallmark of FECD. In addition, we advocate that pharmacological targeting of Nrf2 as a possible therapy for FECD.

Keywords: Cornea; Fuchs' endothelial corneal dystrophy; Nrf2; Oxidative stress.