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De-Quan Li, Daniel Meller, Yunqi Liu, Scheffer C. G. Tseng; Overexpression of MMP-1 and MMP-3 by Cultured Conjunctivochalasis Fibroblasts. Invest. Ophthalmol. Vis. Sci. 2000;41(2):404-410.
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purpose. To determine whether conjunctivochalasis, denoting redundant, loose,
nonedematous inferior bulbar conjunctiva, is associated with increased
expression and activity of matrix metalloproteinases (MMPs) over their
tissue inhibitors (TIMPs).
methods. Expression of transcripts and proteins of MMPs, TIMPs, and urokinase
plasminogen activator (uPA) by cultured normal human conjunctival and
conjunctivochalasis fibroblasts was determined by Northern
hybridization, enzyme-linked immunosorbent assay (ELISA), and Western
blot analysis, respectively. Gelatin and casein zymography and
quantitative collagenase activity assay were performed in the
serum-free conditioned media.
results. Compared with normal conjunctival fibroblasts from six subjects,
conjunctivochalasis fibroblasts from eight patients showed markedly
increased transcript expression of MMP-1 (5- to 32-fold) and MMP-3 (4-
to 30-fold), whereas that of MMP-2, TIMP-1, TIMP-2, and uPA was similar
between the two groups. Protein levels were increased in the serum-free
conditioned media of conjunctivochalasis fibroblasts for MMP-1 (3.5- to
7.6-fold) and MMP-3 (2.3- to 13-fold), determined by ELISA and Western
blot analysis. There was increased caseinolytic activity of MMP-3 and
collagenolytic activity of MMP-1 (2.2-fold) by conjunctivochalasis
fibroblasts, whereas no difference was noted between these two types of
fibroblasts in the protein and gelatinolytic activity of MMP-2 or
expression of TIMP-1 and TIMP-2 proteins, although that of TIMP-1
transcript was slightly higher in some conjunctivochalasis fibroblasts.
No expression of MMP-9 was detected.
conclusions. Overexpression of MMP-1 and MMP-3 mRNA by conjunctivochalasis
fibroblasts is correlated with their increased protein levels and
proteolytic activities. Collectively, these data help explain how
conjunctivochalasis manifests excessive degradation of the conjunctival
matrix and Tenon’s capsule.
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