Collagenase (mmp-1) and timp-1 in destructive corneal disease associated with rheumatoid arthritis

Abstract

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 associatedwith 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 cornealfibrocytes is probably a major mediator of collagen degradation in rheumatoid cornealulceration. In addition, reduced levels of TIMP-1 expression are consistent with collagenase activity and tissue destruction. Epithelial–stromal cell interactions and theproduction of local inflammatory mediators are of major importance in the pathogenesis of corneal destruction, although the precise nature of the antigenic stimulation and/orcellular interactions remains to be elucidated. © 1995 Royal College of Ophthalmologists.