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Reduced expression of apolipoprotein E and immunoglobulin heavy constant gamma 1 proteins in Fuchs endothelial corneal dystrophy
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 OphthalmologyVolume
47Issue
8Pagination
1028-1042ISSN
1442-6404Department/School
Menzies Institute for Medical ResearchPublisher
Blackwell Publishing AsiaPlace of publication
54 University St, P O Box 378, Carlton, Australia, Victoria, 3053Rights statement
© 2019 Royal Australian and New Zealand College of OphthalmologistsRepository Status
- Restricted