Pathomechanismen der Alterung des RPE und prophylaktische Therapieoptionen im Hinblick auf die AMD

Zusammenfassung

Ein intaktes retinales Pigmentepithel (RPE) ist für die Funktion der darüber liegenden neurosensorischen Netzhaut eine zentrale Voraussetzung. In der postmitotischen einlagigen Zellschicht des RPE sind unterschiedlichste Funktionen, wie z. B. Abbau der Photorezeptoraußensegmente, Vitamin-A-Stoffwechsel, Unterstützung des retinalen Metabolismus und Aufrechterhaltung der äußeren Blut-Retina-Schranke vereinigt. Bedingt durch die Belastungen einer hohen Stoffwechselrate, hoher okularer Sauerstoffspiegel, Exposition mit energiereichem kurzwelligem Licht und einer damit verbundenen Bildung von freien Sauerstoffradikalen ist das RPE auf effektive Schutzsysteme angewiesen. Trotz hochdifferenzierter Abwehrmechanismen gegenüber diesem Stress kommt es im Rahmen der Alterung zu einem kumulativen Schaden im RPE, der letztlich als eine wesentliche Teilkomponente in der Pathogenese der altersabhängigen Makuladegeneration zu sehen ist. Das bessere Verständnis dieser Vorgänge wird zur Entwicklung neuer prophylaktischer Ansätze beitragen, die in einer ständig älter werdenden Gesellschaft dringend gebraucht werden.

Abstract

An intact retinal pigment epithelium (RPE) represents an essential condition for the visual process. This post-mitotic RPE monolayer combines different functions such as degradation of photoreceptor outer segments, vitamin A cycle, support of retinal metabolism and maintenance of the outer blood-retina barrier. As a consequence of excessive metabolism, high oxygen levels, exposition to light of short wave length and ensuing radical formation, the RPE is highly dependent on protective systems. In spite of differentiated defence mechanisms, aging processes cause cumulative RPE damage, representing a major component of age-related macular degeneration (AMD), the leading cause of irreversible severe vision loss in people over 50 years old. A better understanding of the underlying pathophysiology will help to develop new prophylactic options which is becoming more and more important with increasing life expectancy.

RPE - Lysosomen - AMD - Lipofuszin - Radikale

retinal pigment epithelium (RPE) - lysosomes - age-related macular degeneration (AMD) - lipofuscin - radicals

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