Collagenolytic Proteinases in Keratoconus
- 1 June 2006
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Cornea
- Vol. 25 (5), 603-610
- https://doi.org/10.1097/01.ico.0000208820.32614.00
Abstract
To study the proteolytic phenomena contributing to the pathogenesis of keratoconus, corneal enzymes with potential to cleave fibrillar collagen were studied. Immunohistochemical labeling was undertaken of conventional and novel mammalian collagenases (MMP-1, -2, -8, -13, and -14) of the matrix metalloproteinase (MMP) family and other collagenolytic proteinases of the serine (human trypsin-2) and cysteine (cathepsin K) endoproteinase families. The results were analyzed using a semiquantitative scoring system. Labeling of MMP-8 was moderate in healthy controls, but weak in keratoconus. Moderate MMP-2 and weak MMP-14 expressions were similar in controls and keratoconus. MMP-1 was slightly overexpressed in keratoconus. In contrast, MMP-13 was weak in controls compared to moderate in keratoconus and human trypsin-2 and cathepsin K were moderate in controls and strong in keratoconus. The collagenolytic milieu of human cornea is more complex than expected. Mesenchymal isoform of MMP-8 (ie, collagenase-2) participates in normal tissue remodeling, which may be impaired in keratoconus. MMP-2 (gelatinase A with interstitial collagenase activity) and MMP-14 (membrane-type MMP type I with collagenolytic potential) seem to be constitutively expressed and probably play a role in normal corneal remodeling. The most prominent changes in keratoconic cornea were observed in collagenase MMP-13 (ie, collagenase-3), and particularly, in cathepsin K and human trypsin-2, which were strongly expressed in keratoconus suggesting a role in intra- and extracellular pathological collagen destruction, respectively. This may contribute to stromal thinning characteristic for keratoconus.Keywords
This publication has 35 references indexed in Scilit:
- EMMPRIN and MMP-1 in KeratoconusCornea, 2006
- Is the corneal degradation in keratoconus caused by matrix‐metalloproteinases?Clinical & Experimental Ophthalmology, 2001
- The architecture of the corneal stromaBritish Journal of Ophthalmology, 2001
- Matrix Metalloproteinase 2: Involvement in KeratoconusEuropean Journal of Ophthalmology, 2000
- Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) and MMP-2 in normal and keratoconus corneasCurrent Eye Research, 2000
- Matrix metalloproteinase (MMP)-9 type IV collagenase/gelatinase implicated in the pathogenesis of Sjögren's syndromeMatrix Biology, 1998
- Membrane Type 1 Matrix Metalloproteinase Digests Interstitial Collagens and Other Extracellular Matrix MacromoleculesOnline Journal of Public Health Informatics, 1997
- Matrix Metalloproteinase-2 Is an Interstitial CollagenaseJournal of Biological Chemistry, 1995
- Human Cathepsin O2, a Novel Cysteine Protease Highly Expressed in Osteoclastomas and Ovary Molecular Cloning, Sequencing and Tissue DistributionBiological Chemistry Hoppe-Seyler, 1995
- Extracellular compartments in matrix morphogenesis: collagen fibril, bundle, and lamellar formation by corneal fibroblasts.The Journal of cell biology, 1984