Abstract
Fuchs endothelial corneal dystrophy (FECD) is a genetically complex, heterogenous, age-related degenerative disease of corneal endothelial cells (CEnCs), occurring in the fifth decade of life with a higher incidence in females. It is characterized by extracellular matrix (ECM) protein deposition called corneal guttae, causing light glare and visual complaints in patients. Corneal transplantation is the only treatment option for FECD patients, which imposes a substantial socioeconomic burden. In FECD, CEnCs exhibit stress-induced senescence, oxidative stress, DNA damage, heightened reactive oxygen species (ROS) production, mitochondrial damage, and dysfunction as well as sustained endoplasmic reticulum (ER) stress. Among all of these, mitochondrial dysfunction involving altered mitochondrial bioenergetics and dynamics plays a critical role in FECD pathogenesis. Extreme stress initiates mitochondrial damage, leading to activation of autophagy, which involves clearance of damaged mitochondria called auto(mito)phagy. In this review, we discuss the role of mitochondrial dysfunction and mitophagy in FECD. This will provide insights into a novel mechanism of mitophagy in post-mitotic ocular cell loss and help us explore the potential treatment options for FECD.
Highlights
The corneal endothelial is the innermost layer of the cornea and plays an important role in maintaining water balance and clarity of the cornea
We have provided an overview of mitochondrial dysfunction and its close relationship with mitophagy in Fuchs endothelial corneal dystrophy (FECD)
Altered mitochondrial bioenergetics such as decreased ATP production, loss of membrane potential (MMP), increased mitochondria reactive oxygen species (ROS) production, and abnormal mitochondrial dynamics such as loss of mitochondrial mass, increased fragmentation, and DNA damage is involved in the pathogenesis of FECD
Summary
The corneal endothelial is the innermost layer of the cornea and plays an important role in maintaining water balance and clarity of the cornea. Fuchs endothelial corneal dystrophy (FECD) is the most common corneal endothelial dystrophy It is a bilateral, genetically heterogeneous degenerative disease of CEnCs occurring in 4% of the U.S population over 40 years of age, with a higher incidence in women [1,2,3,4]. In FECD, CEnCs exhibits stress-induced senescence [8], oxidant-antioxidant imbalance [9], mitochondrial DNA damage [10] and dysfunction [11], sustained unfolded protein response (UPR) [12,13], and endoplasmic reticulum (ER) stress [14] Among these factors, mitochondrial stress [15,16,17,18] plays an important role in FECD pathogenesis. We will review the effects of mitochondrial dysfunction and auto(mito)phagy in CEnCs degeneration seen in FECD and will highlight the importance of mitochondria in developing novel therapeutics for the treatment of FECD
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