Collagenolytic proteinases in keratoconus.
OBJECTIVE
To study the proteolytic phenomena contributing to the pathogenesis of keratoconus, corneal enzymes with potential to cleave fibrillar collagen were studied.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Mackiewicz
Zygmunt
Z
Department of Cell Biology, University of Opole, Opole, Poland.
Määttä
Marko
M
Stenman
Mathias
M
Konttinen
Lasse
L
Tervo
Timo
T
Konttinen
Yrjö T
YT
D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D003315:Cornea / Q000201:enzymology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007640:Keratoconus / Q000201:enzymology* / Q000601:surgery; D015948:Keratoplasty, Penetrating; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism*; D014362:Trypsinogen / Q000378:metabolism*
C064831:PRSS2 protein, human; D014362:Trypsinogen; D002403:Cathepsins; D014357:Trypsin; C534130:CTSK protein, human; D056657:Cathepsin K; D017364:Collagenases; D020782:Matrix Metalloproteinases