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Klin Monbl Augenheilkd 2012; 229(3): 221-226
DOI: 10.1055/s-0031-1282050
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Immunmechanismen bei Netzhautdegeneration

Immune Mechanisms in Retinal Degeneration
M. Karlstetter
,
T. Langmann
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Publication History

08 November 2011

01 December 2011

Publication Date:
01 February 2012 (online)

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Zusammenfassung

Die progrediente Zelldegeneration in der Retina ist die gemeinsame Endstrecke aller erblich bedingten Netzhautdystrophien. Komplex genetische und metabolisch begünstigte Netzhautdegenerationen wie die altersabhängige Makuladegeneration werden ebenfalls maßgeblich durch apoptotische Prozesse bestimmt. Umfangreiche Untersuchungen an verschiedensten Tiermodellen dieser Erkrankungen weisen auf die frühzeitige und meist chronische Aktivierung des angeborenen Immunsystems als gemeinsamen Effektormechanismus hin. Die Komplementkaskade als humorale Säule und Mikrogliazellen als Phagozyten stellen dabei besonders sensible Sensoren und potente Effektoren der retinalen Immunantwort dar. Neben der genetischen Prädisposition beeinflussen verschiedenste individuelle Faktoren wie das Alter oder die Ernährung die Immunhomöostase der Netzhaut. Aufgrund der effektiven Funktionsweise des innaten Immunsystems kann eine lokale chronische Entzündung die Netzhautdegeneration auf verschiedenste Weise perpetuieren. Dieser Artikel fasst den Stand der aktuellen Literatur zur Rolle des angeborenen Immunsystems bei Netzhautdegenerationen zusammen. Er fokussiert dabei besonders auf Hinweise aus Humanstudien und stellt einen Zusammenhang zwischen der Aktivierung des Komplementsystems und der Funktion von Mikroglia in der degenerierenden Netzhaut dar. Daraus abgeleitete Konzepte beschreiben die Immunpathologie der Netzhaut als neues therapeutisches Ziel für eine Neuroprotektion.

Abstract

Hereditary retinal dystrophies are characterised by a common apoptotic pathway leading to progressive retinal degeneration. Similar degenerative processes are evident in multifactorial and complex retinal disorders including age-related macular degeneration. To understand early triggers of these mechanisms, genetic and experimental mouse models have been developed that mimic various forms of human retinal degeneration. In most of these models, early chronic activation of the innate immune system has been documented. This process mainly involves the complement cascade as humoral component and microglial cells as sensors and effectors of the retinal immune response. Current evidence suggests that the genetic predisposition and individual factors like age or diet critically influence the immune homeostasis in the retina. Based on their effectiveness, innate immune mechanisms are thought to support or even provoke retinal degeneration. This review article summarises recent progress in understanding the role of innate immunity in retinal degenerative diseases. We especially focus on human studies and attempt to provide a link between activation of the complement system and microglial function. Moreover, concepts are presented that highlight the retinal immunopathology as potential therapeutic target to prevent vision loss.

Schlüsselwörter

Genetik - Retina - Mikroglia - Komplementsystem - Netzhautdegeneration

Key words

genetics - retina - microglia - complement system - retinal degeneration
 

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