Proteomics of Fuchs' endothelial corneal dystrophy support that the extracellular matrix of Descemet's membrane is disordered.
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 shown to be 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 in both methods. These results support that the morphological changes observed in FECD are caused in part by an aberrant assembly of the extracellular matrix within the Descemet's membrane/endothelial layer.
Department of Molecular Biology and Genetics and ‡Interdisciplinary Nanoscience Center, Aarhus University , 8000 Aarhus, Denmark.
Ebbe Toftgaard
ET
Poulsen
Thomas F
TF
Dyrlund
Kasper
K
Runager
Carsten
C
Scavenius
Toke Peter
TP
Krogager
Peter
P
Højrup
Ida B
IB
Thøgersen
Kristian W
KW
Sanggaard
Henrik
H
Vorum
Jesper
J
Hjortdal
Jan J
JJ
Enghild
D000596:Amino Acids / Q000032:analysis; D002853:Chromatography, Liquid; D003886:Descemet Membrane / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods
D000596:Amino Acids; D016326:Extracellular Matrix Proteins
Descemet’s membrane; Fuchs’ endothelial corneal dystrophy; cornea; extracted ion chromatogram; iTRAQ