title: Resistance of corneal RFUVA–cross-linked collagens and small leucine-rich proteoglycans to degradation by matrix metalloproteinases.
abstract: OBJECTIVE
  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.
authors: Division of Biology, Kansas State University, Manhattan, Kansas 66506-4901, USA. ytz@ksu.edu
authors: Yuntao
authors: Y
authors: Zhang
authors: Xiuli
authors: X
authors: Mao
authors: Tyler
authors: T
authors: Schwend
authors: Stacy
authors: S
authors: Littlechild
authors: Gary W
authors: GW
authors: Conrad
mesh_terms: D000818:Animals; D002417:Cattle; D024042:Collagen Type I / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D007640:Keratoconus / Q000378:metabolism* / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D020782:Matrix Metalloproteinases