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EMMPRIN and MMP-1 in Keratoconus

Seppälä, Hannu P. S. MD*; Määttä, Marko MD; Rautia, Mikko PhD, DSc*; Mackiewicz, Zygmunt PhD, DSc; Tuisku, Ilpo MD; Tervo, Timo MD; Konttinen, Yrjö T. MD, PhD

doi: 10.1097/01.ico.0000183534.22522.39
Basic Investigations

Purpose: This study was conducted to determine the eventual presence and activity of EMMPRIN (extracellular matrix metalloproteinase inducer CD147) and interstitial collagenase MMP-1 in the cornea of keratoconus patients and their eventual interrelationship. MMP-1 was chosen because it is able to degrade fibrillar corneal collagens type I and III and might therefore play a role in stromal thinning in keratoconus.

Methods: Immunohistochemical labeling of EMMPRIN and MMP-1 in relation to histopathological changes in 5 keratoconus patients and 5 matched healthy controls was investigated.

Results: Relatively strong EMMPRIN expression was found in normal corneal epithelial cells, but moderate expression was also found in stroma. In keratoconus, EMMPRIN was found in all layers of cornea, especially in histopathologically altered areas. In normal cornea, MMP-1 staining was weak and restricted to epithelial cells. In keratoconus, MMP-1 expression was slightly augmented in epithelial cells and also appeared locally in a scattered manner in the stroma. The distribution of MMP-1 did not totally overlap with that of histologically apparent corneal damage and EMMPRIN expression.

Conclusions: Both EMMPRIN and MMP-1 are upregulated in keratoconus, but MMP-1 may not be the only tissue destructive MMP upregulated by EMMPRIN as only EMMPRIN expression correlated topologically very well with corneal damage.

From the *Departments of Medicine and †Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland; ‡Department of Ophthalmology, Oulu University Central Hospital and Department of Pathology, University of Oulu, Oulu, Finland; §ORTON Orthopaedic Hospital of the Invalid Foundation Helsinki, Finland and COXA Hospital for the Joint Replacement, Tampere, Finland; and ¶Vilnius University Institute of Experimental and Clinical Medicine, Vilnius, Lithuania.

Received for publication August 12, 2004; revision received July 22, 2005; accepted July 22, 2005.

Reprints: Yrjö T. Konttinen, MD, PhD, Biomedicum Helsinki, P.O. Box 700 (Haartmaninkatu 8), 00029 HUS, Finland (e-mail:

© 2006 Lippincott Williams & Wilkins, Inc.