HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Gottsch, J. D. Articles by Green, W. R. Search for Related Content PubMed PubMed Citation Articles by Gottsch, J. D. Articles by Green, W. R.

Fuchs Corneal Dystrophy: Aberrant Collagen Distribution in an L450W Mutant of the COL8A2 Gene

From the Center for Corneal Genetics, Cornea and External Disease Service, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.

PURPOSE. To characterize histologically Descemet’s membrane in an early-onset Fuchs corneal dystrophy (FCD) COL8A2 mutant and compare these findings with corneas from late-onset FCD and normal corneas.

METHODS. A corneal explant from a patient with the L450W COL8A2 mutation and others with late-onset disease were studied with antibodies to collagens IV, VIIIA1, VIIIA2, fibronectin, and laminin. Transmission electron microscopy was performed on a portion of the explant. Control explants included eye bank corneas without known disease and surgical explants from unrelated conditions.

RESULTS. In normal corneas, a regular array of colocalized COL8A1 and COL8A2 was observed in the anterior half of Descemet’s membrane. In the L450W mutant, Descemet’s membrane was several times thicker than normal and traversed by refractile strands and blebs that stained intensely for COL8A2, a feature also observed in late-onset FCD. Both the 1 and 2 subtypes of collagen VIII were observed at high levels along the anterior edge of Descemet’s, another abnormal feature also found in late-onset FCD. Ultrastructure of the L450W cornea revealed a well-formed anterior banded layer more than three times thicker than normal. An unusual, thin internal layer was rich in patches of wide-spaced collagen. The layer is a distinctive pathologic structure that is associated with FCD and is characterized by 120 nm periodicity and the presence of collagen VIII. Depositions of collagen IV, fibronectin, and laminin were also greatly increased in the of posterior Descemet’s membrane, yet another general feature shared between early- and late-onset disease.

CONCLUSIONS. Early-onset COL8A2 L450W disease involves massive accumulation and abnormal assembly of collagen VIII within Descemet’s membrane, a process that is presumed to begin during fetal development. Both early- and late-onset subtypes of FCD appear to be the result of abnormal basement membrane assembly rather than a primary defect in endothelial metabolism.

This article has been cited by other articles:

				U. V. Jurkunas, M. S. Bitar, I. Rawe, D. L. Harris, K. Colby, and N. C. Joyce Increased Clusterin Expression in Fuchs' Endothelial Dystrophy Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 2946 - 2955. [Abstract] [Full Text] [PDF]

				P Liskova, Q Prescott, S S Bhattacharya, and S J Tuft British family with early-onset Fuchs' endothelial corneal dystrophy associated with p.L450W mutation in the COL8A2 gene Br. J. Ophthalmol., December 1, 2007; 91(12): 1717 - 1718. [Full Text] [PDF]

				L. H. Suh, C. Zhang, R. S. Chuck, W. J. Stark, S. Naylor, K. Binley, S. Chakravarti, and A. S. Jun Cryopreservation and Lentiviral-Mediated Genetic Modification of Human Primary Cultured Corneal Endothelial Cells Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3056 - 3061. [Abstract] [Full Text] [PDF]

				O. H. Sundin, K. W. Broman, H. H. Chang, E. C. L. Vito, W. J. Stark, and J. D. Gottsch A Common Locus for Late-Onset Fuchs Corneal Dystrophy Maps to 18q21.2-q21.32. Invest. Ophthalmol. Vis. Sci., September 1, 2006; 47(9): 3919 - 3926. [Abstract] [Full Text] [PDF]