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Matrix metalloproteinases in human choroidal neovascular membranes excised following verteporfin photodynamic therapy
  1. Olcay Tatar1,
  2. Annemarie Adam2,
  3. Kei Shinoda3,
  4. Tillmann Eckert4,
  5. Gábor B Scharioth5,
  6. Micheal Klein6,
  7. Efdal Yoeruek1,
  8. Karl Ulrich Bartz-Schmidt1,
  9. Salvatore Grisanti1
  1. 1
    University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University, Tuebingen, Germany
  2. 2
    Department of Pathology, Eberhard-Karls University, Tuebingen, Germany
  3. 3
    Laboratory of Visual Physiology, National Institute of Sensory Organs, Tokyo, Japan
  4. 4
    Augenklinik der Staedtischen Kliniken, Frankfurt am Main, Germany
  5. 5
    Augenzentrum Recklinghausen, Germany
  6. 6
    Augenklinik Tausendfensterhaus, Duisburg, Germany
  1. Professor Dr Salvatore Grisanti, University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University, Tuebingen, Germany, Schleichstrasse 12-15, 72076 Tuebingen, Germany; Salvatore.Grisanti{at}


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 49 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, cytokeratin 18, 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<0.001). At longer post-PDT intervals, a significant increase of MMP-9 in stroma (p = 0.037) and of endostatin in RPE–Bruch’s membrane (p = 0.02), vessels (p = 0.005) and stroma (p<0.001) 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.

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  • Funding: This work was supported by grants from the Vision 100 Foundation and Jung Foundation.

  • Competing interests: None.

  • Abbreviations:

    age-related macular degeneration


    choroidal neovascular membranes


    endothelial cell


    extracellular matrix


    matrix metalloproteinases


    photodynamic therapy


    pigment epithelium-derived factor


    vascular endothelial growth factor

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