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, 47, (8) pp. 1028-1042. ISSN 1442-6404 (2019) [Refereed Article]
© 2019 Royal Australian and New Zealand College of Ophthalmologists
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:||Refereed Article|
|Keywords:||Fuchs endothelial corneal dystrophy, apolipoproteins E, immunoglobulin heavy constant gamma 1 protein, proteomics, real-time polymerase chain reaction|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Ophthalmology and optometry|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Burdon, KP (Professor Kathryn Burdon)|
|Web of Science® Times Cited:||4|
|Deposited By:||Menzies Institute for Medical Research|
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