Abstract
Glaucoma is a multifactorial disease and especially mechanisms occurring independently from an elevated intraocular pressure (IOP) are still unknown. Likely, the immune system contributes to the glaucoma pathogenesis. Previously, IgG antibody depositions and retinal ganglion cell (RGC) loss were found in an IOP-independent autoimmune glaucoma model. Therefore, we investigated the possible participation of the complement system in this model. Here, rats were immunized with bovine optic nerve homogenate antigen (ONA), while controls (Co) received sodium chloride (n = 5–6/group). After 14 days, RGC density was quantified on flatmounts. No changes in the number of RGCs could be observed at this point in time. Longitudinal optic nerve sections were stained against the myelin basic protein (MBP). We could note few signs of degeneration processes. In order to detect distinct complement components, retinas and optic nerves were labeled with complement markers at 3, 7, 14, and 28 days and analyzed. Significantly more C3 and MAC depositions were found in retinas and optic nerves of the ONA group. These were already present at day 7, before RGC loss and demyelination occurred. Additionally, an upregulation of C3 protein was noted via Western Blot at this time. After 14 days, quantitative real-time PCR revealed significantly more C3 mRNA in the ONA retinas. An upregulation of the lectin pathway-associated mannose-serine-protease-2 (MASP2) was observed in the retinas as well as in the optic nerves of the ONA group after 7 days. Significantly more MASP2 in retinas could also be observed via Western Blot analyses at this point in time. No effect was noted in regard to C1q. Therefore, we assume that the immunization led to an activation of the complement system via the lectin pathway in retinas and optic nerves at an early stage in this glaucoma model. This activation seems to be an early response, which then triggers degeneration. These findings can help to develop novel therapy strategies for glaucoma patients.
Highlights
Glaucoma is one of the most common causes of blindness worldwide and in 2020 about 79.6 million people will be affected (Quigley and Broman, 2006; EGS, 2014)
To evaluate if the complement system is activated over time, the factors C3 and membrane attack complex (MAC) were immunohistochemically analyzed in retinas 3, 7, 14, and 28 days after immunization
Our group could show that even a moderate increase of intraocular pressure (IOP) leads to an activation of the complement components C3 and MAC (Becker et al, 2015)
Summary
Glaucoma is one of the most common causes of blindness worldwide and in 2020 about 79.6 million people will be affected (Quigley and Broman, 2006; EGS, 2014) This neurodegenerative disease leads to a loss of retinal ganglion cells (RGCs) and their axons, which induces characteristic clinical symptoms, such as gradual visual field loss. In the last few years, abnormal antibody patterns were found in sera of patients with glaucoma (Wax et al, 1994, 2001; Grus et al, 2004) These were characterized as antibodies against ocular tissue (Joachim et al, 2008) and were detected in patients with elevated IOP as well as in patients with normal tension glaucoma. IgG autoantibody depositions were observed in the human glaucomatous retina (Gramlich et al, 2013a) All these findings lead to the question to which extent the immune system is involved in this disease
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