Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) and MMP-2 in normal and keratoconus corneas

Abstract

The observation that MT1-MMP expression may be up-regulated in keratoconus corneas, taken together with the demonstration that human corneal cells can express this enzyme, which in turn can activate latent MMP-2, provide evidence for a possible role for MT1-MMP in the pathogenesis of keratoconus.

Reduced Scleral TIMP-2 Expression Is Associated With Myopia Development: TIMP-2 Supplementation Stabilizes Scleral Biomarkers of Myopia and Limits Myopia Development

“…41,42 Incubation with the plant lectin con-A led to the activation of MMP-2 in tree shrew skin cells as has been reported for other fibroblast cells, including human corneal, dermal, and gingival fibroblasts. [42][43][44] This activation occurred at similar con-A concentrations to those reported for corneal fibroblasts. 44 The activation mechanism of con-A is thought to be via the MT1-MMP-mediated pathway.…”

Quantitative analysis of corneal microstructure in keratoconus utilising in vivo confocal microscopy

“…49 This is supported by the nonuniform proteoglycan distribution within the stroma. 50 The production of abnormal substances within the keratoconic stroma previously has been reported: with abnormal production of matrix metalloproteinase-2; 51 upregulation of the expression of MT1-MMP; 52 overexpression of keratocan; 53 reduction in expression of type X11 collagen 54 and modification of type V1 collagen synthesis 55 all being documented. Although keratocytes appear to provide a vital role in the stability of the corneal structure, 17 perhaps the corneal changes exhibited by keratoconics are due to substances synthesised or expressed by keratocytes.…”

Keratoconus Layer by Layer - Pathology and Matrix Metalloproteinases

“…In another study, keratoconic immunolabelling for MMP-1, -2 and -3 resembled that of the normal cornea and post LASIK keratectasia 61 while peroxidase immunohistochemistry performed by Collier's group showed that MMP-14 was significantly elevated in the keratoconic stroma 55 .…”

“…Collier et al performed peroxidase immunohistochemistry and determined that MMP-14 (MT1-MMP) was significantly elevated in the epithelium of keratoconic corneas compared to eye bank controls, while MMP-2 was not 55 . This was surprising given that MMP-14 was previously shown to activate latent MMP-2 as well as being able to degrade matrix molecules directly.…”

“…This was surprising given that MMP-14 was previously shown to activate latent MMP-2 as well as being able to degrade matrix molecules directly. MMP-14 forms a tri-molecular complex on the cell surface with MMP-2 and TIMP-2 in a complex sequence 55 . The timing of this interaction and concentrations of component molecules determine whether the MMP-14 active site is exposed and available for MMP-2 activation and matrix degradation 55 .…”