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O. Tatar, K. Shinoda, A. Adam, K. Lucke, C. Eckardt, P. Stalmans, T. Eckerdt, S. Bopp, K. Bartz–Schmidt, S. Grisanti; Impact of Verteporfin Photodynamic Therapy on Endostatin Expression and Angiogenesis in Human Choroidal Neovascular Membranes . Invest. Ophthalmol. Vis. Sci. 2006;47(13):873.
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© ARVO (1962-2015); The Authors (2016-present)
Endostatin is an endogeneous angiogenesis inhibitor which requires E–selectin for its anti–angiogenic activity. We aimed to evaluate the impact of photodynamic therapy (PDT) on the expression of endostatin with regard to E–selectin and vascular endothelial growth factor (VEGF) in human choroidal neovascular membranes (CNVM) secondary to age–related macular degeneration (AMD).
Retrospective review of an interventional case series of sixty–eight patients (sixty–eight eyes) who underwent removal of CNVM. Twenty–nine patients were treated with PDT 3 to 655 days prior to surgery. CNVM were stained for CD34, CD105, Ki–67, cytokeratin 18, endostatin, E–selectin and VEGF. Thirty–nine CNVM without previous treatment were used as controls. "Predominance score of VEGF over endostatin" (PS) is defined for RPE, endothelial cells (EC) and stroma of each membrane calculating the difference between VEGF and endostatin staining scores in each component. Immunohistological results were correlated with the clinical findings.
CNVM without pre–treatment disclosed different degrees of endostatin, E–selectin and VEGF expression by EC, RPE and stroma. Four CNVM treated by PDT 3 days previously, disclosed severely damaged EC and low proliferative activity (median:4.85, range:0–78.76 nuclei/mm2). Predominance score of VEGF over endostatin was significantly higher in RPE (median PS=2.5) and stroma (median PS=2) in comparison to the control group (median PS=0 both in RPE and stroma) (p=0.0044, p=0.003, respectively). At longer post–PDT intervals, CNVM disclosed significantly decreased predominance score of VEGF over endostatin in RPE (median PS=0) and stroma (median PS=0) (p= 0.0131, p=0.0152, respectively) but still healthy, activated EC and significantly increased proliferative activity (median:114.12; range:0–955.2 nuclei/mm2) (p=0.0227). PDT did not show a significant impact on E–selectin.
Chronologically late appearance of endostatin with consequent VEGF predominance early after PDT seems to cause the clinical finding of recurrence in longer post–PDT intervals. Therefore, early combination of PDT with antiangiogenic adjuvants may increase its effectiveness.
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