Extracellular matrix alterations in late-onset Fuchs' corneal dystrophy.
OBJECTIVE
To characterize the alterations of extracellular matrix proteins in Descemet's membranes (DM) of patients with late-onset Fuchs' corneal dystrophy (FCD) and to differentiate them from nonspecific alterations in pseudophakic bullous keratopathy (PBK).


METHODS
Human DM-endothelial cell complexes were obtained from patients with late-onset FCD (n = 40), PBK (n = 6), and control eyes (n = 5). Gene expression profiles of endothelial cells were compared using a commercial real-time PCR array and quantitative real-time PCR assays for confirmation of differentially expressed genes. A total of 24 extracellular matrix proteins were also localized in cryosections of corneal specimens from FCD (n = 10), PBK (n = 4), and control eyes (n = 5) by immunohistochemistry.


RESULTS
Polymerase chain reaction array analysis revealed a significant upregulation of 27 out of 84 extracellular matrix-related genes including collagens, proteoglycans, glycoproteins, cell adhesion molecules, and matrix metalloproteinases in FCD specimens as compared to normal controls, which could be partly confirmed and quantified by real-time PCR. Comparative analysis of FCD and PBK specimens showed a significant and consistent FCD-specific upregulation of collagen types I, III, and XVI; fibronectin; agrin; clusterin; transforming growth factor beta-induced (TGFBI); and integrin α4 (3- to 18-fold, P < 0.05). Immunohistochemistry revealed an increased labeling of collagen (types III, VII, XV, XVI), agrin, fibulin-2, TGFBI, versican, and clusterin in the DM of FCD specimens compared to PBK specimens.


CONCLUSIONS
The findings provide evidence for a specific upregulation, production, and deposition of collagen types III and XVI, agrin, TGFBI, and clusterin in late-onset FCD and thus point to the importance of matrix alterations in the pathophysiology of FCD.
Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Julia M
JM
Weller
Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Matthias
M
Zenkel
Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Ursula
U
Schlötzer-Schrehardt
Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Bjoern O
BO
Bachmann
Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Theofilos
T
Tourtas
Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Friedrich E
FE
Kruse
D000368:Aged; D004247:DNA / Q000235:genetics*; D003886:Descemet Membrane / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors
D016326:Extracellular Matrix Proteins; D004247:DNA
Descemet's membrane; Fuchs' corneal dystrophy; corneal endothelial cells; extracellular matrix; pseudophakic bullous keratopathy