Proteomics of Fuchs' Endothelial Corneal Dystrophy support that the extracellular matrix of Descemet's membrane is disordered

Ebbe Toftgaard Poulsen, Thomas F Dyrlund, Kasper Runager, Carsten Scavenius, Toke Peter Krogager, Peter Højrup, Ida B Thøgersen, Kristian Wejse Sanggaard, Henrik Vorum, Jesper Hjortdal, Jan Johannes Enghild

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Fuchs' endothelial corneal dystrophy (FECD) is a major corneal disorder affecting the innermost part of the cornea, leading to visual impairment. As the morphological changes in FECD are mainly observed in the extracellular matrix of the Descemet's membrane/endothelial layer we determined the protein profiles of diseased and control tissues using two relative quantitation MS methods. The first quantitation method based on the areas of the extracted ion chromatograms, quantified the 51 and 48 most abundant proteins of the Descemet's membrane/endothelial layer in patient and control tissues, respectively, of which 10 were significantly regulated. The results indicated that the level of type VIII collagen was unaltered even though the protein previously has been implicated in familial early onset forms of the disease. Using the second relative quantitation method iTRAQ we identified 22 differentially regulated proteins, many of which are extracellular proteins known to be involved in proper assembly of the basement membrane in other tissues. In total 26 differentially regulated proteins were identified, of which 6 proteins were regulated by both methods. These results support that the morphological changes observed in FECD is caused in part by an aberrant assembly of the extracellular matrix within the Descemet's membrane/endothelial layer.

Original languageEnglish
JournalJournal of Proteome Research
Volume13
Issue number11
Pages (from-to)4659–4667
ISSN1535-3893
DOIs
Publication statusPublished - 7. Nov 2014

Bibliographical note

Publication Date (Web): May 21, 2014

Keywords

  • extracted ion chromatogram
  • cornea
  • iTRAQ
  • Descemets membrane
  • Fuchs endothelial corneal dystrophy
  • Humans
  • Tandem Mass Spectrometry/methods
  • Male
  • Descemet Membrane/metabolism
  • Extracellular Matrix Proteins/metabolism
  • Fuchs' Endothelial Dystrophy/metabolism
  • Amino Acids/analysis
  • Chromatography, Liquid
  • Proteomics/methods
  • Female
  • Gene Expression Regulation/physiology

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