S100B immunization triggers NFκB and complement activation in an autoimmune glaucoma model

Abstract

In glaucoma, latest studies revealed an involvement of the complement system with and without an elevated intraocular pressure. In the experimental autoimmune glaucoma model, immunization with antigens, such as S100B, lead to retinal ganglion cell (RGC) loss and optic nerve degeneration after 28 days. Here, we investigated the timeline of progression of the complement system, toll-like-receptor 4 (TLR4), and the transcription factor nucleus factor-kappa B (NFκB). Therefore, rats were immunized with S100B protein (S100) and analyzed at 3, 7, and 14 days. RGC numbers were comparable at all points in time, whereas a destruction of S100 optic nerves was noted at 14 days. A significant increase of mannose binding lectin (MBL) was observed in S100 retinas at 3 days. Subsequently, significantly more MBL+ cells were seen in S100 optic nerves at 7 and 14 days. Accordingly, C3 was upregulated in S100 retinas at 14 days. An increase of interleukin-1 beta was noted in S100 aqueous humor samples at 7 days. In this study, activation of complement system via the lectin pathway was obvious. However, no TLR4 alterations were noted in S100 retinas and optic nerves. Interestingly, a significant NFκB increase was observed in S100 retinas at 7 and 14 days. We assume that NFκB activation might be triggered via MBL leading to glaucomatous damage.

Transfer of the Experimental Autoimmune Glaucoma Model from Rats to Mice—New Options to Study Glaucoma Disease

“…This led to a loss of RGCs and optic nerve degeneration [2,3,4]. Additionally, an enhanced activation of glia cells and complement system proteins could be observed [4,5,6,7,8]. Furthermore, a remodeling of extracellular matrix proteins was noted [9].…”

Derzeitiger Stand zur primären Neuroprotektion beim Glaukom

“…Auch hier fand eine Aktivierung des Komplementsystems über den Lektinweg statt. Vermehrte Ablagerungen von MBL zeigten sich sogar schon nach 3 Tagen in den Retinae und nach 7 sowie 14 Tagen auch in den Sehnerven [27]. Auch hier kam es zu einer Initiierung des Komplementsystems bevor ein Verlust der RGZ detektiert werden konnte.…”

Glaukom im Fokus

“…In diesem Modell kommt durch die Immunisierung mit okulären Antigenen nach 4 Wochen zum retinalen Ganglienzellsterben und zur Degeneration des Sehnervens ohne IOD-Anstieg [10]. Es konnte weiterhin gezeigt werden, dass es in dem Modell zu vermehrten Ablagerungen von MAC sowohl in der Retina als auch in den Sehnerven 7 Tage nach Immunisierung kommt [11,12]. Diese frühe Aktivierung der terminalen Komponenten des Komplementsystems könnte beim späteren Zelluntergang eine wichtige Rolle spielen.…”