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

• Published in: Scientific reports 2018-06, Vol.8 (1), p.9821-12, Article 9821
• Main Authors: Reinehr, Sabrina, Reinhard, Jacqueline, Gandej, Marcel, Gottschalk, Ivo, Stute, Gesa, Faissner, Andreas, Dick, H. Burkhard, Joachim, Stephanie C.
• Format: Article
• Language: English
• Subjects: 13/51; 14/63; 38/77; 692/420; 692/699; Antigens; Complement activation; Complement component C3; Degeneration; Glaucoma; Humanities and Social Sciences; Immunization; Interleukin 1; Mannose; multidisciplinary; NF-κB protein; Nuclei; Optic nerve; Retina; Retinal ganglion cells; S100b protein; Science; Science (multidisciplinary); TLR4 protein; Toll-like receptors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-28183-6

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.