Keratoconus: Matrix metalloproteinase-2 activation and TIMP modulation

VA Smith, FJ Matthews, MA Majid, SD Cook

Research output: Contribution to journalArticle (Academic Journal)peer-review

44 Citations (Scopus)


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 [3H]Type IV collagen and analysed by zymography. Optimally maintained and nutrient deprived cells were subsequently incubated with [3H]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.
Translated title of the contributionKeratoconus: Matrix metalloproteinase-2 activation and TIMP modulation
Original languageEnglish
Pages (from-to)431 - 439
Number of pages9
JournalBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Volume1762 (4)
Publication statusPublished - Apr 2006

Bibliographical note

Publisher: Elsevier


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