Immunreaktionen beim Glaukom

Zusammenfassung

Das Glaukom ist eine der häufigsten Ursache der Erblindung weltweit. Nach geltender Definition beschreibt der Begriff Glaukom eine Gruppe okulärer Erkrankungen, die zu einem fortschreitenden Verlust retinaler Ganglienzellen mit nachfolgenden typischen glaukomatösen Gesichtsfeldausfällen führen. Der intraokuläre Druck (IOD) wird zwar weiter als wichtigster Risikofaktor gewertet, seine Senkung halbiert das Risiko der Krankheitsprogression, stoppt sie aber nicht vollständig. Allerdings entwickelt eine Vielzahl von Patienten ein Glaukom, ohne dass ein erhöhter IOD bei ihnen vorliegt. Dies sind Hinweise darauf, dass der erhöhte IOD nicht die einzige Ursache der glaukomatösen Schädigung sein kann. Aktuell werden insbesondere der Mangel neurotropher Faktoren, eine vaskuläre Schädigung, Glutamattoxizität und Gliaaktivierung als Faktoren der Krankheitsentstehung diskutiert. Neben den bereits genannten Theorien rückt auch eine Beteiligung des Immunsystems immer mehr in den Mittelpunkt der Diskussion. Unsere Arbeitsgruppe konnte in vielen Untersuchungen des Serums und Kammerwassers von Glaukompatienten veränderte Immunreaktionen von Autoantikörpern gegen verschiedene Proteine nachweisen, so etwa gegen Hitzeschockproteine (HSP), α-Fodrin, saures Gliafaserprotein (GFAP) und Myelin-basisches Protein (MBP) und gegen Vimentin. In vitro konnte gezeigt werden, dass Antikörper gegen kleine Hitzeschockproteine die Apoptose retinaler Ganglienzellen (RGZ) auslösen können. Im experimentellen Autoimmun-Glaukomtiermodell kam es nach Immunisierung mit dem Hitzeschockprotein27 zu einem apoptotischen Untergang retinaler Ganglienzellen. Unklar ist, ob diese immunologischen Veränderungen Ursache oder Folge der Erkrankung sind. Unabhängig davon kann eine Veränderung in den Antikörperprofilen gegen okuläre Antigene als Grundlage einer diagnostischen Analyse verwendet werden, bevor sich die ersten klinischen Zeichen einer Glaukomerkrankung zeigen.

Abstract

Glaucoma is one of the most common causes of irreversible blindness worldwide. The pathogenesis of the disease is not fully understood. Elevated intraocular pressure is still considered to be one of the most important risk factors, but cannot explain all cases of glaucoma disease. The involvement of autoimmune mechanisms may play an important role in the pathogenesis of glaucoma. Evidence to support this theory has been shown by our group in previous studies: glaucoma patients were found to develop antibody alterations against specific retina and optic nerve proteins. In the experimental autoimmune glaucoma model, we demonstrated that an immunisation with these proteins causes retinal ganglion cell loss in an autoimmune context. In spite of these results, it is still unclear whether the changes in antibody patterns have a causal connection with glaucoma development or are merely an epiphenomena of the disease. However, these changes in the natural autoimmunity offer a new approach to gain deeper insight into glaucoma pathophysiology and to develop a diagnostic approach for early diagnosis.

Schlüsselwörter

Glaukom - Autoimmunität - Proteomics - natürliche Autoimmunität - Autoantikörper

Key words

glaucoma - autoimmunity - proteomics - natural autoimmunity - autoantibodies

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