Matrix metalloproteinases in human choroidal neovascular membranes excised following verteporfin photodynamic therapy

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. N eovascular age-related macular degeneration (AMD) is the leading cause of visual loss in older people in the western world.

Doxycycline's Effect on Ocular Angiogenesis: An In Vivo Analysis

“…The neovascularization (NV) associated with many ocular diseases including diabetic retinopathy, macular degeneration, pterygium and corneal transplant rejection is responsible for much morbidity, including blindness. Vascular endothelial growth factor (VEGF) and matrix metalloproteinases are elevated in exudative age-related macular degeneration (AMD) 1–3. This disease contributes to a significant decline in quality of life, secondary to choroidal neovascularization and submacular hemorrhage.…”

In vitro and in vivo matrix metalloproteinase expression after photodynamic therapy with a liposomal formulation of aminolevulinic acid and its methyl ester

“…It was confirmed that three days after PDT with verteporfin, MMP-9 expression was significantly weaker in the stroma and at longer post-PDT intervals, a significant increase in MMP-9 in the RPE-Bruch's membrane, vessels and stroma was disclosed, whereas MMP-2 expression did not significantly change. It was assumed that PDT induced an early decrease in MMP-9 expression and an increase at longer intervals [23]. In another study, it was shown that in keratinocyte supernatants, after PDT the levels of MMP-1 and MMP-3 were not significantly altered.…”

“…The MMP-2 expression was not significantly changed. Thus, it was assumed that PDT induced an early decrease in MMP-9 expression, and at longer intervals, an increase possibly associated with angiogenic processes responsible for recurrence after PDT [23]. In earlier studies, the role of photofrin-mediated PDT in eliciting the expression of MMPs and modulators of MMP activity and in the activation of vascularendothelial growth factor (VEGF) and COX-2-derived prostaglandins was evaluated.…”

Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles

“…Evidence exists that MMP-2 and MMP-9 are involved in the involution and regression of the vessels in the later stages of angiogenesis (32).…”