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Reduced expression of apolipoprotein E and immunoglobulin heavy constant gamma 1 proteins in Fuchs endothelial corneal dystrophy
Author(s) -
Kuot Abraham,
Ronci Maurizio,
Mills Richard,
Klebe Sonja,
Snibson Grant,
Wiffen Steven,
Loh Raymond,
Corbett Mark,
Zhou Tiger,
Chataway Tim,
Burdon Kathryn P.,
Craig Jamie E.,
Urbani Andrea,
Sharma Shiwani
Publication year - 2019
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/ceo.13569
Subject(s) - corneal endothelium , pathogenesis , medicine , proteomics , endothelium , immunohistochemistry , apolipoprotein e , gene expression , antibody , membrane protein , pathology , microbiology and biotechnology , cornea , biology , ophthalmology , gene , immunology , disease , membrane , biochemistry
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‐MS E ) 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.