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Reduced expression of apolipoprotein E and immunoglobulin heavy constant gamma 1 proteins in Fuchs endothelial corneal dystrophy

journal contribution
posted on 2023-05-20, 05:27 authored by Kuot, A, Ronci, M, Mills, R, Klebe, S, Snibson, G, Wiffen, S, Loh, R, Corbett, M, Zhou, T, Chataway, T, Kathryn BurdonKathryn Burdon, Craig, JE, Urbani, A, Sharma, S
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.

History

Publication title

Clinical and Experimental Ophthalmology

Volume

47

Issue

8

Pagination

1028-1042

ISSN

1442-6404

Department/School

Menzies Institute for Medical Research

Publisher

Blackwell Publishing Asia

Place of publication

54 University St, P O Box 378, Carlton, Australia, Victoria, 3053

Rights statement

© 2019 Royal Australian and New Zealand College of Ophthalmologists

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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