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Keratoconus: matrix metalloproteinase-2 activation and TIMP modulation.
V A Smith1, F J Matthews, M A Majid
1University of Bristol, Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK. Val.Smith@bristol.ac.uk
Biochimica Et Biophysica Acta
|March 7, 2006
Summary
Keratoconus progression may be linked to increased matrix metalloproteinase-2 (MMP-2) in corneal stromal cells. This study found higher MMP-2 in early keratoconus, suggesting a role for MMP-2 in this ocular disease.
Area of Science:
- Ophthalmology
- Cell Biology
- Biochemistry
Background:
- Keratoconus is an eye condition characterized by corneal thinning, cone formation, and scarring.
- The role of matrix metalloproteinase-2 (MMP-2) and its inhibitor (TIMP) in keratoconus pathogenesis is not fully understood.
Purpose of the Study:
- To compare the MMP-2/TIMP systems in stromal cells from normal and keratoconic corneas.
- To investigate the impact of nutrient deprivation on MMP-2 activation and cell survival in keratoconic stromal cells.
Main Methods:
- Established stromal cell cultures from normal, clear keratoconic (KCS-1), and scarred keratoconic (KCS-2) corneas.
- Assayed secreted MMP-2 using radiolabeled collagen and zymography.
- Quantified secreted radiolabeled macromolecules after nutrient deprivation.
Main Results:
- KCS-1 stromal cells produced more MMP-2 than normal cells, without increased TIMP production.
- Nutrient deprivation induced MMP-2 activation and cell death in KCS-1 cells.
- KCS-2 cells showed balanced MMP-2 and TIMP-1 expression, with TIMP-1 protecting against cell death.
Conclusions:
- Overexpression of MMP-2 without compensatory TIMP increase in KCS-1 cells may drive keratoconus progression.
- TIMP-1 upregulation in surviving KCS-1 cells and KCS-2 cells suggests a protective role in mitigating disease.
- These findings highlight the critical balance of MMP-2 and TIMP in maintaining corneal health and disease progression.