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Overexpression of Collagenase (MMP-1) and Stromelysin (MMP-3) by Pterygium Head Fibroblasts
De-Quan Li, MD, PhD;
Sao-Bing Lee, MD;
Zeenat Gunja-Smith, PhD;
Yunqi Liu;
Abraham Solomon, MD;
Daniel Meller, MD;
Scheffer C. G. Tseng, MD, PhD
Arch Ophthalmol. 2001;119:71-80.
Background The balance between matrix metalloproteinases (MMPs) and the tissue
inhibitors of metalloproteinases (TIMPs) determines the extent of connective
tissue degradation and remodeling.
Objective To determine whether pterygium, characterized by fibrovascular invasion
into the cornea, may in part be mediated by an increased activity of MMPs.
Materials and Methods Expression of transcripts and proteins of MMPs, TIMPs, and urokinase
plasminogen activator (uPA) by cultured human pterygium head, body, and subconjunctival
fibroblasts, and normal corneal and conjunctival fibroblasts were determined
by Northern hybridization, enzyme-linked immunosorbent assay, Western blotting,
zymography, and quantitative collagenase assay, respectively.
Results Compared with normal conjunctival fibroblasts from 6 subjects, the expression
of MMP-1 and MMP-3 transcripts was dramatically increased in pterygium head
fibroblasts of 8 patients, but not in pterygium body fibroblasts of 6 patients.
The protein levels and collagenolytic and caseinolytic activities of MMP-1
and/or MMP-3 were also markedly increased in pterygium head fibroblasts. The
MMP-1 and MMP-3 proteins and activity decreased in order 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 previously 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 corneal invasion.
From the Ocular Surface and Tear Center, Department of Ophthalmology,
Bascom Palmer Eye Institute (Drs Li, Lee, Solomon, Meller and Tseng), and
Departments of Medicine (Dr Gunja-Smith and Ms Liu) and Cell Biology and Anatomy
(Dr Tseng), University of Miami School of Medicine, Miami, Fla.
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