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S.M. Michels, U. Schlötzer-Schrehard, G.O. Naumann, U. Schmidt-Erfurth; Photodynamic Therapy Induces Expression of Vascular Endothelial Growth Factor (VEGF) and Pigment Epithelial Derived Factor (PEDF) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2157.
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Purpose:To evaluate the influence of photodynamic therapy (PDT) on the regulation of vascular endothelial growth factor (VEGF), VEGF receptor 3 (VEGFR-3) and pigment epithelium derived factor (PEDF) in aged eyes. Methods:PDT using verteporfin with the recommended standard parameters was applied to selected areas of the macular region in eyes of elderly patients. Eyes which were scheduled for surgical removal due to untreatable malignancy served as study eyes (n=4). Age-matched donor eyes were used as controls (n=4). Lesions were classified by ophthalmoscopy, fluorescein (FA) and indocyanine green angiography (ICGA) as well as LM/EM histology. Immunohistology using antibodies against VEGF, VEGFR-3 and PEDF was performed in PDT-treated areas, untreated collateral areas in study eyes and untreated areas of control eyes. Specimen were fixed in 4% paraformaldehyde/1% glutaraldehyde and embedded in paraffine. 4 µm thick sections were stained using the peroxidase labeled streptavidin-biotin method. Results:All study eyes demonstrated a characteristic hypofluorescence of the treated area by FA/ICGA. Selective damage at the level of choriocapillary endothelial cells was documented by LM/EM histology. VEGF labeling was positive in vascular endothelia of the choriocapillary layer and focally within larger choroidal vessels in treated areas, but was absent in untreated controls. Areas showing VEGF expression also demonstrated upregulation of VEGF receptor 3. PEDF expression was present in the retinas of all eyes whether they were treated or not. However, PEDF expression by choroidal endothelial cells was specific for treated areas of study eyes only. Conclusions: PDT using verteporfin induces a characteristic angiogenic response in the retina and choroid of human eyes. Enhanced expression of VEGF, VEGF receptor 3 and PEDF appears to be associated with PDT and was documented in normal choroidal endothelial cells following treatment.
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