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Matrix metalloproteinases in human choroidal neovascular membranes excised following verteporfin photodynamic therapy
  1. Olcay Tatar (olcaytatar{at}yahoo.com),
  2. Annemarie Adam,
  3. Kei Shinoda,
  4. Tillmann Eckert,
  5. Gábor B Scharioth,
  6. Michael Klein,
  7. Efdal Yoeruek,
  8. Karl U Bartz-Schmidt,
  9. Salvatore Grisanti (salvatore.grisanti{at}med.uni-tuebingen.de)
  1. University Eye Hospital at the Centre for Ophthalmology of the Eberhard-Karls University, Tuebingen, Germany
  2. Department of Pathology, Eberhard-Karls University, Tuebingen, Germany
  3. Laboratory of Visual Physiology, National Institute of Sensory Organs, Tokyo, Japan
  4. Augenklinik der Staedtischen Kliniken, Frankfurt am Main, Germany
  5. Augenzentrum Recklinghausen, Germany
  6. Augenklinik Tausendfensterhaus, Duisburg, Germany
  7. University Eye Hospital at the Centre for Ophthalmology of the Eberhard-Karls University, Tuebingen, Germany
  8. University Eye Hospital at the Centre for Ophthalmology of the Eberhard-Karls University, Tuebingen, Germany
  9. Eberhard-Karls University Tuebingen, Germany

    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.

    • Age-related macular degeneration
    • Choroidal neovascularization
    • Endostatin
    • Matrix Metalloproteinases
    • Verteporfin Photodynamic Therapy

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