Collagenase (MMP-1) and TIMP-1 in destructive corneal disease associated with rheumatoid arthritis

Eye (Lond). 1995:9 ( Pt 6):703-18. doi: 10.1038/eye.1995.182.


The aim of the study was to immunolocalise interstitial collagenase (MMP-1) and the tissue inhibitor of metalloproteinases (TIMP-1) in ulcerating corneas from patients with rheumatoid arthritis, to determine whether changes in expression are associated with destructive corneal disease. Collagenase was expressed by stromal cells in 8 of 8 ulcerating corneas but was not seen in normal tissue (n = 3). TIMP-1 was abundant throughout the normal stroma, but was much reduced or absent from diseased corneas. Collagenase staining was frequently more intense near the epithelial surface and associated with a cellular infiltrate consisting of activated antigen-presenting cells (HLA-DR+), many of which were macrophages (CD68+) and derived from the epithelium or limbus (S100+). Interstitial collagenase produced by infiltrating macrophages and/or stimulated corneal fibrocytes is probably a major mediator of collagen degradation in rheumatoid corneal ulceration. In addition, reduced levels of TIMP-1 expression are consistent with collagenase activity and tissue destruction. Epithelial-stromal cell interactions and the production of local inflammatory mediators are of major importance in the pathogenesis of corneal destruction, although the precise nature of the antigenic stimulation and/or cellular interactions remains to be elucidated.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigen-Presenting Cells / enzymology
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / enzymology*
  • Child, Preschool
  • Collagenases / metabolism*
  • Cornea / enzymology
  • Cornea / pathology
  • Corneal Ulcer / complications
  • Corneal Ulcer / enzymology*
  • Corneal Ulcer / pathology
  • Female
  • Glycoproteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Macrophages / enzymology
  • Male
  • Matrix Metalloproteinase 1
  • Matrix Metalloproteinase Inhibitors
  • Metalloendopeptidases / metabolism*
  • Middle Aged
  • Tissue Inhibitor of Metalloproteinases


  • Glycoproteins
  • Matrix Metalloproteinase Inhibitors
  • Tissue Inhibitor of Metalloproteinases
  • Collagenases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 1