Active matrilysin (MMP-7) in human pterygia: Potential role in angiogenesis

PURPOSE. Pterygia are invasive, proliferative fibrovascular growths, with t he matrix metalloproteinase (MMP) family of enzymes strongly implicated in the pathogenesis of these lesions. The purpose of this study was to determi ne the cellular distribution and activation status of matrilysin (MMP-7) in pterygia. METHODS. Resected pterygia (n = 8) and normal conjunctiva (n = 8) were sect ioned and analyzed immunohistochemically with two different epitope-specifi c anti-MMP-7 monoclonal antibodies (Abs) which differentiate pro- and activ e MMP-7. The specificity of each Ab was confirmed by Western blot analysis of p-aminophenylmercuric acetate (APMA)-activated and latent recombinant MM P-7. Pterygia (n = 4) and autologous normal conjunctiva (n = 4) were placed in organ culture to determine the activation status of secreted MMP-7. RESULTS. Precursor and active forms of MMP-7 were detected in epithelial ce lls from both pterygia and normal conjunctiva. Intense immunoreactivity for pro- and active MMP-7 was also observed in the pterygium vasculature, but was essentially absent from conjunctival vessels. Pro-MMP-7 was also identi fied in the epithelial basement membrane and associated with matrix compone nts in pterygia. The 141-7B2 Ab reacted with the 30-kDa latent MMP-7, and t he IM47L Ab precipitated a 19-kDa active enzyme, thus confirming the differ ential specificity of each Ab. Pro- and active MMP-7 were increased 1.4- an d 2.7-fold, respectively, in the supernatants from organ-cultured pterygia compared with conjunctiva. CONCLUSIONS. This study is the first to specifically localize an active MMP species in pterygia and strengthens the hypothesis that these enzymes are involved in the pathogenesis of this disease. The data also suggest that MM P-7 may play a significant role in the angiogenesis that characterizes this lesion. Future studies will be directed at determining whether targeting M MP activity may be useful for treatment of pterygia.