Document Detail

Fuchs corneal dystrophy: aberrant collagen distribution in an L450W mutant of the COL8A2 gene.
MedLine Citation:
PMID:  16303941     Owner:  NLM     Status:  MEDLINE    
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 alpha1 and alpha2 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 approximately 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.
John D Gottsch; Cheng Zhang; Olof H Sundin; W Robert Bell; Walter J Stark; W Richard Green
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  46     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-11-23     Completed Date:  2006-01-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4504-11     Citation Subset:  IM    
Center for Corneal Genetics, Cornea and External Disease Service, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
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MeSH Terms
Collagen Type IV / metabolism*
Collagen Type VIII / genetics,  metabolism*
Descemet Membrane / metabolism,  pathology
Fibronectins / metabolism
Fluorescent Antibody Technique, Indirect
Fuchs' Endothelial Dystrophy / genetics,  metabolism*,  pathology
Laminin / metabolism
Microscopy, Confocal
Reg. No./Substance:
0/COL8A2 protein, human; 0/Collagen Type IV; 0/Collagen Type VIII; 0/Fibronectins; 0/Laminin

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