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Resistance of corneal RFUVA-cross-linked collagens and small leucine-rich proteoglycans to degradation by matrix metalloproteinases

Zhang, Yuntao, Mao, Xiuli, Schwend, Tyler, Littlechild, Stacy Lee and Conrad, Gary W. 2013. Resistance of corneal RFUVA-cross-linked collagens and small leucine-rich proteoglycans to degradation by matrix metalloproteinases. Investigative Ophthalmology and Visual Science 54 (2) , pp. 1014-1025. 10.1167/iovs.12-11277

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Purpose. Extracellular matrix metalloproteinases (MMPs) are thought to play a crucial role in corneal degradation associated with the pathological progression of keratoconus. Currently, corneal cross-linking by riboflavin and ultraviolet A (RFUVA) has received significant attention for treatment of keratoconus. However, the extent to which MMPs digest cross-linked collagen and small leucine-rich proteoglycans (SLRPs) remains unknown. In this study, the resistance of RFUVA–cross-linked collagens and SLRPs to MMPs has been investigated. Methods. To investigate the ability of MMPs to digest cross-linked collagen and SLRPs, a model reaction system using purified collagen type I, type IV, and nonglycosylated, commercially available recombinant SLRPs, keratocan, lumican, mimecan, decorin, and biglycan in solution in vitro has been compared using reactions inside an intact bovine cornea, ex vivo. Results. Our data demonstrate that corneal cross-linked collagen type I and type IV are resistant to cleavage by MMP-1, MMP-2, MMP-9, and MMP-13, whereas non–cross–linked collagen I, IV, and natively glycosylated SLRPs are susceptible to degradation by MMPs. In addition, both cross-linked SLRPs themselves and cross-linked polymers of SLRPs and collagen appear able to resist degradation. These results suggest that the interactions between SLRPs and collagen caused by RFUVA protect both SLRPs and collagen fibrils from cleavage by MMPs. Conclusions. A novel approach for understanding the biochemical mechanism whereby RFUVA cross-linking stops keratoconus progression has been achieved.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
Additional Information: Confirmation received by publisher on 21 February 2014 that publisher's pdf can be self-archived 6 months after publication.
Publisher: Association for Research in Vision and Ophthalmology
ISSN: 0146-0404
Date of First Compliant Deposit: 30 March 2016
Last Modified: 12 Jun 2019 02:55

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