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Abstract

Background: Fuchs endothelial corneal dystrophy (FECD) is a progressive and potentially a sight threatening disease, and a common indication for corneal grafting in the elderly. Aberrant thickening of Descemet's membrane, formation of microscopic excrescences (guttae) and gradual loss of corneal endothelial cells are the hallmarks of the disease. The aim of this study was to identify differentially abundant proteins between FECD-affected and unaffected Descemet's membrane.Methods: Label-free quantitative proteomics using nanoscale ultra-performance liquid chromatography-mass spectrometry (nUPLC-MSE ) was employed on affected and unaffected Descemet's membrane extracts, and interesting findings were further investigated using quantitative reverse transcription-polymerase chain reaction and immunohistochemical techniques.Results: Quantitative proteomics revealed significantly lower abundance of apolipoprotein E (APOE) and immunoglobulin heavy constant gamma 1 protein (IGHG1) in affected Descemet's membrane. The difference in the distribution of APOE between affected and unaffected Descemet's membrane and of IGHG1 detected by immunohistochemistry support their down-regulation in the disease. Comparative gene expression analysis showed significantly lower APOE mRNA levels in FECD-affected than unaffected corneal endothelium. IGHG1 gene is expressed at extremely low levels in the corneal endothelium, precluding relative expression analysis.Conclusions: This is the first study to report comparative proteomics of Descemet's membrane tissue, and implicates dysregulation of APOE and IGHG1 proteins in the pathogenesis of Fuchs endothelial corneal dystrophy.

Item Type:	Article
Authors/Creators:	Kuot, A and Ronci, M and Mills, R and Klebe, S and Snibson, G and Wiffen, S and Loh, R and Corbett, M and Zhou, T and Chataway, T and Burdon, KP and Craig, JE and Urbani, A and Sharma, Shiwani
Keywords:	Fuchs endothelial corneal dystrophy, apolipoproteins E, immunoglobulin heavy constant gamma 1 protein, proteomics, real-time polymerase chain reaction
Journal or Publication Title:	Clinical and Experimental Ophthalmology
Publisher:	Blackwell Publishing Asia
ISSN:	1442-6404
DOI / ID Number:	10.1111/ceo.13569
Copyright Information:	© 2019 Royal Australian and New Zealand College of Ophthalmologists
Related URLs:	Google Scholar: Burdon, KP UTAS Profile: Burdon, KP
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