Die Wirkung der VEGF-A-Antagonisten auf molekularer und zellulärer Ebene

Zusammenfassung

Die Therapie der Neutralisierung des VEGF-A hat sich in der klinischen Routine zur Behandlung der feuchten altersbedingten Makuladegeneration etabliert, Indikationserweiterungen sind kontinuierlich hinzugekommen. Drei verschiedene Substanzen haben sich bewährt. In der Anwendung an dem sehr heterogenen Patientenkollektiv werden jedoch Unterschiede in der Effektivität, wie Nonresponder oder Rezidive, und individuelle Anwendungseffekte diskutiert. Hier könnten die unterschiedlichen molekularen Strukturen der 3 angewandten Substanzen von Bedeutung sein. Daher fasst dieser Artikel die Daten der unterschiedlichen molekularen und zellulären Effekte der 3 Substanzen zusammen und versucht, deren Relevanz zu bewerten. Neben Gemeinsamkeiten, wie vergleichbaren Affinitäten zum VEGF-A, ergeben sich Unterschiede, darunter die Fähigkeit, nicht nur VEGF-A zu neutralisieren, oder die Stabilität der VEGF-A-Molekülkomplexe. Auf der Ebene der molekularen Eigenschaften wie auch der zellulären Effekte besteht allerdings eine nur geringe Vergleichbarkeit der Studien, es existieren z. T. widersprüchliche Daten, oder die Daten sind nicht durch mehrere unabhängige Studien abgesichert. Daher sind auf dieser Basis keine Unterschiede in den klinischen Eigenschaften vorhersagbar.

Abstract

Anti-VEGF-A therapy is successfully established as a routine therapy to treat wet age-related macular degeneration. Indications have been extended to other retinal diseases. Three different substances have been demonstrated to be active. However, the efficacy of these substances is highly variable in heterogeneous groups of patients and may include non-responders and relapses, so that there may be very individual treatment effects. It is speculated that differences in the molecular properties or structures of the three substances might explain these observations. This article therefore summarises the recent publications on this topic and discusses their relevance. Apart from common features such as VEGF-A affinity, the substances exhibit differences, including the stability of the VEGF-A/molecule complexes and the ability to neutralise angiogenic molecules other than only VEGF-A. At the cellular level, a variety of different methods have been used and the results are often inconsistent. It is therefore not yet possible to predict the clinical properties of VEGF-A neutralising substances on the basis of their known molecular properties or cellular effects.

Schlüsselwörter

Aflibercept - Ranibizumab - Bevacizumab - Endothelzellen - Pigmentepithel

Key words

aflibercept - ranibizumab - bevacizumab - endothelial cells - retinal pigment epithelium

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