Document Detail

Keratoconus: matrix metalloproteinase-2 activation and TIMP modulation.
MedLine Citation:
PMID:  16516444     Owner:  NLM     Status:  MEDLINE    
Keratoconus is an ocular condition that causes corneal thinning, cone formation and scarring. In view of a hypothesis that activated MMP-2 may initiate or facilitate disease progression, the MMP-2/TIMP systems of stromal cells derived from normal and keratoconic corneas have been compared. To achieve this, stromal cell cultures were established from normal, clear keratoconic (KCS-1) and scarred keratoconic (KCS-2) corneas. The secreted MMP-2 was assayed using [(3)H]Type IV collagen and analysed by zymography. Optimally maintained and nutrient deprived cells were subsequently incubated with [(3)H]lysine. The secreted radiolabelled macromolecules were separated and quantified. The results obtained indicated that optimally maintained KCS-1 stromal cells produced more MMP-2 than normal stromal cells but not TIMP. Nutrient deprivation induced MMP-2 activation and cell death. Surviving cells upregulated TIMP-1 synthesis and in this respect became similar to the KCS-2 stromal cells that did not excessively generate activated MMP-2 or die as a consequence of nutrient deprivation. From these results, it was concluded that KCS-1 stromal cells over-expressed MMP-2 without increasing TIMP production. This may facilitate MMP-2 activation in vivo and hence advance the keratoconic condition. KCS-2 cultures over-expressed both MMP-2 and TIMP-1. Because TIMP-1 inhibits MMP-2 activity and protects against cell death it may be of significance in initiating repair processes and curtailing keratoconus.
V A Smith; F J Matthews; M A Majid; S D Cook
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-02-17
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1762     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-13     Completed Date:  2006-05-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  431-9     Citation Subset:  IM    
University of Bristol, Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK.
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MeSH Terms
Cells, Cultured
Cornea / cytology,  enzymology*
Culture Media, Serum-Free
Enzyme Activation
Enzyme Precursors / metabolism
Gelatinases / metabolism
Keratoconus / enzymology*,  pathology
Matrix Metalloproteinase 2 / metabolism*
Metalloendopeptidases / metabolism
Stromal Cells / cytology,  enzymology
Tissue Inhibitor of Metalloproteinase-1 / metabolism
Tissue Inhibitor of Metalloproteinases / metabolism*
Reg. No./Substance:
0/Culture Media, Serum-Free; 0/Enzyme Precursors; 0/Tissue Inhibitor of Metalloproteinase-1; 0/Tissue Inhibitor of Metalloproteinases; EC 3.4.24.-/Gelatinases; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.-/progelatinase; EC Metalloproteinase 2

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