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Decorin and biglycan of normal and pathologic human corneasPURPOSE: Corneas with scars and certain chronic pathologic conditions contain highly sulfated dermatan sulfate, but little is known of the core proteins that carry these atypical glycosaminoglycans. In this study the proteoglycan proteins attached to dermatan sulfate in normal and pathologic human corneas were examined to identify primary genes involved in the pathobiology of corneal scarring. METHODS: Proteoglycans from human corneas with chronic edema, bullous keratopathy, and keratoconus and from normal corneas were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), quantitative immunoblotting, and immunohistology with peptide antibodies to decorin and biglycan. RESULTS: Proteoglycans from pathologic corneas exhibit increased size heterogeneity and binding of the cationic dye alcian blue compared with those in normal corneas. Decorin and biglycan extracted from normal and diseased corneas exhibited similar molecular size distribution patterns. In approximately half of the pathologic corneas, the level of biglycan was elevated an average of seven times above normal, and decorin was elevated approximately three times above normal. The increases were associated with highly charged molecular forms of decorin and biglycan, indicating modification of the proteins with dermatan sulfate chains of increased sulfation. Immunostaining of corneal sections showed an abnormal stromal localization of biglycan in pathologic corneas. CONCLUSIONS: The increased dermatan sulfate associated with chronic corneal pathologic conditions results from stromal accumulation of decorin and particularly of biglycan in the affected corneas. These proteins bear dermatan sulfate chains with increased sulfation compared with normal stromal proteoglycans.
Document ID
20040172578
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Funderburgh, J. L.
(Kansas State University Manhattan 66506-4901, United States)
Hevelone, N. D.
Roth, M. R.
Funderburgh, M. L.
Rodrigues, M. R.
Nirankari, V. S.
Conrad, G. W.
Date Acquired
August 22, 2013
Publication Date
September 1, 1998
Publication Information
Publication: Investigative ophthalmology & visual science
Volume: 39
Issue: 10
ISSN: 0146-0404
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: EY09368
CONTRACT_GRANT: EY00952
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Developmental Biology

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