Reduced expression of apolipoprotein E and immunoglobulin heavy constant gamma 1 proteins in Fuchs endothelial corneal dystrophy
| Autor: | Maurizio Ronci, Shiwani Sharma, Grant R. Snibson, Jamie E Craig, Abraham Kuot, Tiger Zhou, Tim Chataway, Kathryn P. Burdon, Steven Wiffen, Andrea Urbani, Richard A. Mills, Raymond Loh, Sonja Klebe, Mark A. Corbett |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Adult Male Proteomics Corneal endothelium immunoglobulinheavy constant gamma 1 protein genetic structures Quantitative proteomics Real-Time Polymerase Chain Reaction Mass Spectrometry Pathogenesis 03 medical and health sciences 0302 clinical medicine Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA Gene expression Medicine Humans RNA Messenger Chromatography High Pressure Liquid Aged Aged 80 and over biology business.industry Fuchs' Endothelial Dystrophy Middle Aged Molecular biology Immunohistochemistry eye diseases Ophthalmology 030104 developmental biology Gene Expression Regulation 030221 ophthalmology & optometry biology.protein Female sense organs Antibody business Carrier Proteins apolipoproteins E |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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