Matrix metalloproteinases in human choroidal neovascular membranes excised following verteporfin photodynamic therapy
- Olcay Tatar (olcaytatar{at}yahoo.com),
- Annemarie Adam,
- Kei Shinoda,
- Tillmann Eckert,
- Gábor B Scharioth,
- Michael Klein,
- Efdal Yoeruek,
- Karl U Bartz-Schmidt,
- Salvatore Grisanti (salvatore.grisanti{at}med.uni-tuebingen.de)
- University Eye Hospital at the Centre for Ophthalmology of the Eberhard-Karls University, Tuebingen, Germany
- Department of Pathology, Eberhard-Karls University, Tuebingen, Germany
- Laboratory of Visual Physiology, National Institute of Sensory Organs, Tokyo, Japan
- Augenklinik der Staedtischen Kliniken, Frankfurt am Main, Germany
- Augenzentrum Recklinghausen, Germany
- Augenklinik Tausendfensterhaus, Duisburg, Germany
- University Eye Hospital at the Centre for Ophthalmology of the Eberhard-Karls University, Tuebingen, Germany
- University Eye Hospital at the Centre for Ophthalmology of the Eberhard-Karls University, Tuebingen, Germany
- Eberhard-Karls University Tuebingen, Germany
- Published Online First 2 May 2007
Abstract
Aim: To evaluate expression of proangiogenic matrix metalloproteinases (MMP) 2 and 9 at distinct intervals after verteporfin photodynamic therapy (PDT) in human choroidal neovascular membranes (CNV) secondary to age-related macular degeneration (AMD).
Methods: Retrospective review of an interventional case series of forty-nine patients who underwent removal of CNV. Twenty-six patients were treated with PDT 3 to 383 days prior to surgery. Twenty-three CNV without previous treatment were used as controls. CNV were stained for CD34, cytokeratin18, endostatin, MMP-2 and MMP-9 by immunohistochemistry.
Results: CNV without previous therapy disclosed MMP-2, MMP-9 in RPE-Bruch's membrane, vessels and stroma in different intensities. Three days after PDT, MMP-9 expression was significantly weaker in stroma (p=0.0019). Endostatin was significantly reduced in vessels (p=0.0005). At longer post-PDT intervals, a significant increase of MMP-9 in stroma (p=0.0373) and of endostatin in RPE-Bruch's membrane (p=0.02), vessels (p=0.005) and stroma (p=0.0007) were disclosed. No significant changes in MMP-2 expression were detected.
Conclusions: PDT induced an early, temporary decrease in MMP-9 and endostatin expression. At longer intervals, MMP-9 increase is possibly associated with the angiogenic process responsible for recurrence after PDT. MMP-9, however, acts as a double-edged sword by concomitant induction of endostatin, an endogenous inhibitor of angiogenesis.
