eCite Digital Repository

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

Citation

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, S, Reduced expression of apolipoprotein E and immunoglobulin heavy constant gamma 1 proteins in Fuchs endothelial corneal dystrophy, Clinical and Experimental Ophthalmology pp. 1-15. ISSN 1442-6404 (2019) [Refereed Article]

Copyright Statement

2019 Royal Australian and New Zealand College of Ophthalmologists

DOI: doi:10.1111/ceo.13569

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 Details

Item Type:Refereed Article
Keywords:Fuchs endothelial corneal dystrophy, apolipoproteins E, immunoglobulin heavy constant gamma 1 protein, proteomics, real-time polymerase chain reaction
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
ID Code:133788
Year Published:2019
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-07-10
Last Modified:2019-08-05
Downloads:0

Repository Staff Only: item control page