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The role of nonenzymatic glycation and carbonyls in collagen cross-linking for the treatment of keratoconus

Brummer, Gage, Littlechild, Stacy Lee, McCall, Scott, Zhang, Yuntao and Conrad, Gary W. 2011. The role of nonenzymatic glycation and carbonyls in collagen cross-linking for the treatment of keratoconus. Investigative Ophthalmology and Visual Science 52 (9) , pp. 6363-6369. 10.1167/iovs.11-7585

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Abstract

Purpose. Corneal cross-linking (CXL) is a treatment for keratoconus that eliminates the need for keratoplasty in most patients. However, its molecular mechanisms remain under study. Advanced glycation end products (AGEs) have been suggested by many studies as the causative strengthening agent during CXL, though no studies to date have directly tested this hypothesis. Methods. Corneas of young rabbits and sharks were pretreated with pyridoxal hydrochloride and copper ions before CXL. Two known inhibitors of AGE formation, aminoguanidine and rifampicin, were applied during CXL in the treatment solution. Tensile strength tests were conducted after these experiments to detect diminished or accentuated corneal stiffening after CXL. SDS-PAGE was performed on type I collagen cross-linked in the absence and presence of AGE inhibitors. Results. Pretreatment with pyridoxal hydrochloride resulted in significantly higher corneal stiffening after CXL. AGE inhibitors significantly diminished cross-linking as detected by both tensile strength measurements using whole corneas and gel electrophoresis of in vitro cross-linking of type I collagen in solution, in the presence and absence of the inhibitors. Rifampicin inhibited CXL more significantly than aminoguanidine in gel electrophoresis and tensile strength tests, confirming recent findings on its efficacy as an AGE inhibitor. Conclusions. Data presented here suggest that CXL is carbonyl dependent and involves the formation of AGE cross-links. Six possible cross-linking mechanisms are discussed.

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
URI: http://orca-mwe.cf.ac.uk/id/eprint/53693

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