Matrix metalloproteinases in human choroidal neovascular membranes excised following verteporfin photodynamic therapy.
OBJECTIVE
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.
Tatar
Olcay
O
University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University, Tuebingen, Germany.
Adam
Annemarie
A
Shinoda
Kei
K
Eckert
Tillmann
T
Scharioth
Gábor B
GB
Klein
Micheal
M
Yoeruek
Efdal
E
Bartz-Schmidt
Karl Ulrich
KU
Grisanti
Salvatore
S
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000201:enzymology* / Q000209:etiology / Q000601:surgery; D043169:Endostatins / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008268:Macular Degeneration / Q000150:complications / Q000601:surgery; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011166:Porphyrins / Q000627:therapeutic use; D012189:Retrospective Studies; D000077362:Verteporfin
D015415:Biomarkers; D043169:Endostatins; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9