Overexpression of collagenase (MMP-1) and stromelysin (MMP-3) by pterygiumhead fibroblasts

Background: The balance between matrix metalloproteinases (MMPs) and the ti ssue inhibitors of metalloproteinases (TIMPs) determines the extent of conn ective tissue degradation and remodeling. Objective: To determine whether pterygium, characterized by fibrovascular i nvasion into the cornea, may in part be mediated by an increased activity o f MMPs. Materials and Methods: Expression of transcripts and proteins of MMFs, TIMP s, and urokinase plasminogen activator (uPA) by cultured human pterygium he ad, body, and subconjunctival fibroblasts, and normal corneal and conjuncti val fibroblasts were determined by Northern hybridization, enzyme-linked im munosorbent assay, Western blotting, zymography, and quantitative collagena se assay, respectively. Results: Compared with normal conjunctival fibroblasts from 6 subjects, the expression of MMP-1 and MMP-3 transcripts was dramatically increased in pt erygium head fibroblasts of 8 patients, but not in pterygium body fibroblas ts of 6 patients. The protein levels and collagenolytic and caseinolytic ac tivities of MMP-1 and/or MMP-3 were also markedly increased in pterygium he ad fibroblasts. The MMP-1 and MMP-3 proteins and activity decreased in orde r from pterygium head to body to subconjunctival fibroblasts. There was no difference in the transcript and protein expression of MMP-2, TIMP-1, TIMP- 2, and uPA among these groups. Conclusion: Pterygium head fibroblasts express increased mRNA, protein, and activities of MMP-1 and MMP-3. Clinical Relevance: Overexpression of MMP-1 and MMP-3, a phenotype previous ly linked with UV exposure in dermal fibroblasts to explain the pathologic finding of elastotic degeneration, suggests that pterygium head fibroblasts might be intrinsically altered by UV, which might be responsible for corne al invasion.