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.