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Sabrina Reinehr, Marcel Gandej, Gesa Stute, H Burkhard Dick, Stephanie C Joachim; Altered complement expression in the optic nerves of an autoimmune glaucoma model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2528.
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© ARVO (1962-2015); The Authors (2016-present)
Latest studies showed a contribution of the immune system, especially the complement system, in glaucoma. We previously noted complement activation in retinas of the experimental autoimmune glaucoma model (EAG) already before a loss of retinal ganglion cells occurred. Hence, we investigated the activation of the complement system in the optic nerves in this model.
Rats were immunized with optic nerve homogenate (ONA) or S100 protein. Controls received sodium chloride. Longitudinal optic nerve sections (3, 7, 14 days; n=6-8/group) were stained with H&E and LFB and analyzed via a scoring system. Also, the myelin binding protein (MBP) was labeled. To evaluate complement expression, sections were stained with C3, membrane attack complex (MAC) and mannose-associated-serine-protease2 (MASP2). Co-localization of MAC and microglia cells (Iba1) was additionally assessed. Cells were counted with ImageJ. Statistic was performed using one-way ANOVA followed by Dunnett’s test.
No cell infiltrations were noted in the optic nerves in all groups at all points in time (p>0.05). Also, the LFB staining showed no alterations (p>0.05). An increase of MBP was noted in the ONA (p=0.03) and the S100 group (p=0.02) at 3 days. At 7 days, MBP levels went back to control values. A decrease of MBP was observed in the ONA group at 14 days (p=0.03). Regarding C3 and MAC, no alterations were noted in both immunized groups after 3 days (p>0.05). At 7 days, significantly more C3+ and MAC+ cells could be observed in the ONA group (C3: p=0.02; MAC: p<0.001), while no changes were noted in the S100 group. Additionally, MAC+ cells were co-localized with microglia. At 14 days, no differences were noted in regard to C3 and MAC in both immunized groups. For MASP2, no changes were observed in the ONA and S100 group at 3 days (p>0.05). In the ONA group, significantly more MASP2 was noted at 7 days (p=0.04). No alterations were found in the S100 group (p>0.05). At 14 days, MASP2 level in the ONA group went back to control level, the S100 group was still unaffected (p>0.05).
In accordance with our previous results we noted an activation of the complement system via the lectin pathway already before degenerative effects occurred. The complement components seem to be synthesized by microglia cells. We assume that the initiation leads to apoptosis through enhanced cytokine signaling, which induces an activation of caspase 3.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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