title: Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in the human lens: implications for cortical cataract formation.
abstract: OBJECTIVE
  To characterize the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in human cortical cataract and to determine whether there is a correlation with the localization of cortical cataract. To evaluate the expression and activity of MMPs and TIMPs after cytokine and UV-B exposure in a human lens epithelial cell line.
  
  
  METHODS
  Twenty-eight human donor eyes with cortical cataract and 21 normal human donor eyes were photographed. Thirteen cortical cataract and six normal lenses were immunohistochemically analyzed for MMP-1, -2, -3, and -9 and TIMP-1, -2, and -3. Twelve fresh cortical cataract and 12 normal lenses were divided into quadrants to quantify, by ELISA, the expression of MMP-1, -2, -3, and -9 and TIMP-1. Three fresh cortical cataract and three control lenses were assessed for MMP-1, -2, and -9 activity by SDS-PAGE zymography. Human lens epithelial cells (HLE-SRA-01/04) were exposed to proinflammatory cytokines and UV-B radiation to determine the protein expression profiles of MMP-1, -2, -3, and -9 and TIMP-1 and -2.
  
  
  RESULTS
  Immunohistochemical analysis revealed specific localization of MMP-1 within lens epithelium and cortical lens fibers of cortical cataract. Normal lenses had equally low MMP-1, -2, -3, and -9 and TIMP-1, -2, and -3 immunoreactivity, expression, and activity in all lens quadrants. IL-1 and TNF-alpha upregulated the expression of MMP-2, -3, and -9, and UV-B upregulated the expression of MMP-1 in the SRA-01/04 HLE cell line.
  
  
  CONCLUSIONS
  This is the first study to localize the expression of MMP-1 in cataracts with clinically observed opacification in vivo and to examine the expression induced by UV-B, in vitro.
authors.affiliation: Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Nitin H
authors.initials: NH
authors.lastname: Sachdev
authors.forename: Nick
authors.initials: N
authors.lastname: Di Girolamo
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Nolan
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McCluskey
authors.forename: Denis
authors.initials: D
authors.lastname: Wakefield
authors.forename: Minas T
authors.initials: MT
authors.lastname: Coroneo
mesh_terms: D000328:Adult; D002386:Cataract / Q000378:metabolism* / Q000473:pathology; D018929:Cell Culture Techniques; D002470:Cell Survival; D016207:Cytokines / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007904:Lens Cortex, Crystalline / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D014466:Ultraviolet Rays; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases