Collagenase (MMP-1) and TIMP-1 in destructive corneal disease associated with rheumatoid arthritis.
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.
Riley
G P
GP
Rheumatology Research Unit, Addenbrooke's Hospital, Cambridge, UK.
Harrall
R L
RL
Watson
P G
PG
Cawston
T E
TE
Hazleman
B L
BL
D000368:Aged; D000938:Antigen-Presenting Cells / Q000201:enzymology; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000201:enzymology*; D002675:Child, Preschool; D017364:Collagenases / Q000378:metabolism*; D003315:Cornea / Q000201:enzymology / Q000473:pathology; D003320:Corneal Ulcer / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000201:enzymology; D008297:Male; D020781:Matrix Metalloproteinase 1; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D008666:Metalloendopeptidases; D020781:Matrix Metalloproteinase 1