Related Experiment Videos
Active matrilysin (MMP-7) in human pterygia: potential role in angiogenesis
N Di Girolamo1, M T Coroneo, D Wakefield
1Inflammation Research Unit, School of Pathology, University of New South Wales, Sydney, New South Wales, Australia. n.digirolamo@unsw.edu.au
Purpose:
Pterygia are invasive, proliferative fibrovascular growths, with the matrix metalloproteinase (MMP) family of enzymes strongly implicated in the pathogenesis of these lesions. The purpose of this study was to determine the cellular distribution and activation status of matrilysin (MMP-7) in pterygia.
Methods:
Resected pterygia (n = 8) and normal conjunctiva (n = 8) were sectioned and analyzed immunohistochemically with two different epitope-specific anti-MMP-7 monoclonal antibodies (Abs) which differentiate pro- and active MMP-7. The specificity of each Ab was confirmed by Western blot analysis of p-aminophenylmercuric acetate (APMA)-activated and latent recombinant MMP-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 cells 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 identified in the epithelial basement membrane and associated with matrix components in pterygia. The 141-7B2 Ab reacted with the 30-kDa latent MMP-7, and the IM47L Ab precipitated a 19-kDa active enzyme, thus confirming the differential specificity of each Ab. Pro- and active MMP-7 were increased 1.4- and 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 MMP-7 may play a significant role in the angiogenesis that characterizes this lesion. Future studies will be directed at determining whether targeting MMP activity may be useful for treatment of pterygia.
Insights
Active matrilysin (MMP-7) was found in pterygium vasculature, suggesting a role for this matrix metalloproteinase in pterygium pathogenesis and angiogenesis. Targeting MMP-7 may offer a future treatment strategy for this eye condition.
Area of Science:
- Ophthalmology
- Molecular Biology
- Biochemistry
Background:
- Pterygia are fibrovascular growths where matrix metalloproteinases (MMPs) are implicated.
- Matrilysin (MMP-7) is a key enzyme in the MMP family.
Purpose of the Study:
- To investigate the cellular distribution and activation status of matrilysin (MMP-7) in pterygia.
- To understand MMP-7's role in pterygium pathogenesis.
Main Methods:
- Immunohistochemistry was used to detect pro- and active MMP-7 in pterygia and conjunctiva.
- Western blot analysis confirmed antibody specificity for MMP-7 forms.
- Organ culture assessed secreted MMP-7 activation.
Main Results:
- Both precursor and active MMP-7 were present in pterygium epithelial cells.
- Active MMP-7 was significantly detected in pterygium vasculature, unlike conjunctival vessels.
- Organ culture showed increased pro- and active MMP-7 in pterygia compared to conjunctiva.
Conclusions:
- This study first localizes active MMP-7 in pterygia, supporting its role in disease pathogenesis.
- MMP-7 may be crucial for the angiogenesis characteristic of pterygia.
- Targeting MMP activity could be a potential therapeutic approach for pterygia.