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Klin Monbl Augenheilkd 2004; 221(12): 1026-1032
DOI: 10.1055/s-2004-813851
Klinische Studie

© Georg Thieme Verlag KG Stuttgart · New York

Expression angiogener Faktoren durch photodynamische Therapie

Expression of Angiogenic Factors by Photodynamic TherapyM. Rudolf1 , S. Michels2 , U. Schlötzer-Schrehardt3 , U. Schmidt-Erfurth2
  • 1Universitätsklinikum Schleswig-Holstein, Augenklinik Campus Kiel
  • 2Universitätsklinik für Augenheilkunde und Optometrie, Wien, Österreich
  • 3Universitäts-Augenklinik Erlangen
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Publication History

Eingegangen: 2.7.2004

Angenommen: 25.10.2004

Publication Date:
15 December 2004 (online)

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Zusammenfassung

Hintergrund: Der Einfluss der photodynamischen Therapie (PDT) auf die Regulation von Angiogenesefaktoren (vascular endothelial growth factor [VEGF] und pigment epithelium derived factor [PEDF]) wird in menschlichen Augen untersucht. Methode: Augen von Patienten mit unbehandelbarem malignen Melanomen der Peripherie und Indikation zur Enukleation dienten als Studienaugen (n = 2), altersentsprechende Spenderaugen wurden als Kontrolle (n = 2) verwendet. Verteporfin-PDT mit den empfohlenen Standardparametern wurde an intakten Netzhaut- und Aderhautarealen des hinteren Pols appliziert. Nach einer Woche wurden die Behandlungsareale ophthalmologisch, Fluoreszein-(FA-) und Indocyaningrün-(ICGA-)angiographisch untersucht. Postoperativ wurden die Studienaugen lichtmikroskopisch (LM) und elektronenmikroskopisch (EM) analysiert. Eine Immunhistochemie mit spezifischen Antikörpern gegen VEGF und PEDF wurde in PDT-behandelten Arealen und unbehandelten Arealen von Studienaugen sowie in unbehandelten Arealen von Kontrollaugen durchgeführt. Ergebnisse: Alle PDT-behandelten Areale zeigten eine charakteristische chorioidale Hypofluoreszenz in der FA/ICGA. LM- und EM-histologisch zeigte sich eine selektive Schädigung der choriokapillaren Endothelzellen. Eine reproduzierbare Expression von VEGF war ausschließlich in den choriokapillaren Gefäßendothelien PDT-behandelter Areale sowie fokal in größeren Chorioideagefäßen nachweisbar. Die Aderhaut von unbehandelten Arealen der Studienaugen oder Kontrollaugen war VEGF-negativ. PEDF wurde in der Netzhaut und dem RPE aller Augen exprimiert, jedoch konnte nur in den choriokapillaren Gefäßendothelien PDT-behandelter Areale PEDF nachgewiesen werden. Schlussfolgerungen: PDT mit Verteporfin induziert nicht nur strukturelle und angiographische, sondern auch biologische Effekte in menschlichen Augen. VEGF- und PEDF-Expression in Endothelien der Chorioidea infolge PDT sind dokumentierbar und beeinflussen unmittelbar den Heilungsverlauf nach Therapie.

Abstract

Purpose: The purpose of this study was to evaluate the impact of photodynamic therapy (PDT) on the regulation of angiogenic factors such as vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in human eyes. Methods: Eyes of patients with untreatable malignancy served as the study eyes (n = 2), age-matched donor eyes were used as controls (n = 2). Standard Verteporfin-PDT was applied to intact areas of the posterior pole. One week after PDT the eyes were examined by ophthalmoscopy as well as fluorescein (FA) and indocyanine green angiography (ICGA). After enucleation the eyes were processed for LM/EM histology. Immunolabeling using specific antibodies against VEGF and PEDF was performed in PDT-treated areas, untreated collateral areas of study eyes and untreated areas of control eyes. Results: All PDT-treated areas demonstrated a typical choroidal hypofluorescence on FA/ICGA. In LM/EM histology a selective damage of choriocapillary endothelial cells was found. VEGF expression was localized only to choriocapillary endothelial cells and focally in larger choroidal vessels of PDT-treated areas. Untreated areas of study eyes and controls were VEGF-negative. PEDF staining was observed in retinas and RPE of all eyes, but only choroidal endothelial cells of PDT-treated areas showed a PEDF-positive reactivity. Conclusion: PDT not only induces structural and angiographic, but also biological effects in human eyes. VEGF and PEDF expression can be documented in choroidal endothelial cells following PDT and could have an impact on the recovery process after treatment.

Schlüsselwörter

Photodynamische Therapie - Angiogenese - vascular endothelial growth factor

Key words

Photodynamic therapy - angiogenesis - vascular endothelias growth factor

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Prof. Dr. med. U. Schmidt-Erfurth

Universitätsklinik für Augenheilkunde und Optometrie

Währinger Gürtel 18 - 20/8 i

1090 Wien

Österreich

Phone: ++ 43/1/4 04 00-79 31

Fax: ++ 43/1/4 04 00-79 32

Email: ursula.schmidt-erfurth@meduniwien.ac.at