Article Text

PDF
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}med.uni-tuebingen.de

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 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.

Statistics from Altmetric.com

Footnotes

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

  • Competing interests: None.

  • Abbreviations:
    AMD

    age-related macular degeneration

    CNV

    choroidal neovascular membranes

    EC

    endothelial cell

    ECM

    extracellular matrix

    MMP

    matrix metalloproteinases

    PDT

    photodynamic therapy

    PEDF

    pigment epithelium-derived factor

    VEGF

    vascular endothelial growth factor

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • BJO at a glance
    Creig Hoyt