Abstract
The inner layer of the cornea, the corneal endothelium, is post-mitotic and unable to regenerate if damaged. The corneal endothelium is one of the most transplanted tissues in the body. Fuchs’ endothelial corneal dystrophy (FECD) is the leading indication for corneal endothelial transplantation. FECD is thought to be an age-dependent disorder, with a major component related to oxidative stress. Prdx6 is an antioxidant with particular affinity for repairing peroxidised cell membranes. To address the role of Prdx6 in corneal endothelial cells, we used a combination of biochemical and functional studies. Our data reveal that Prdx6 is expressed at unusually high levels at the plasma membrane of corneal endothelial cells. RNAi-mediated knockdown of Prdx6 revealed a role for Prdx6 in lipid peroxidation. Furthermore, following induction of oxidative stress with menadione, Prdx6-deficient cells had defective mitochondrial membrane potential and were more sensitive to cell death. These data reveal that Prdx6 is compartmentalised in corneal endothelial cells and has multiple functions to preserve cellular integrity.
Highlights
The cornea is a transparent refractive structure at the front of the eye
We report that high levels of Prdx6 can be isolated from the plasma membrane of Corneal endothelial cells (CEnCs)
Prdx6 in a corneal endothelium (CE) cell line, we demonstrate that Prdx6 is required to maintain both lipid peroxidation as well as cell viability through the regulation of mitochondrial function
Summary
The cornea is a transparent refractive structure at the front of the eye. The cornea is approximately500 μm thick and composed of several layers, including a protective outer epithelial cell layer; an acellular Bowman’s layer; a stromal layer; an acellular Descemet’s membrane; and a single uniform layer of cells on the posterior surface, termed the corneal endothelium (CE) [1,2,3]. The cornea is a transparent refractive structure at the front of the eye. The CE is essential for maintaining corneal hydration and optimal corneal transparency. This is achieved through a pump-leak mechanism: nutrients from the aqueous humor are allowed to passively diffuse through the ‘leaky’ endothelium into the stroma and, concurrently, an ionic pump drives fluid from the stroma into the aqueous humor. This dynamic ‘barrier and pump’ function serves to maintain corneal hydration and transparency vital for visual acuity
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