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Intravitreal S100B Injection Triggers a Time-Dependent Microglia Response in a Pro-Inflammatory Manner in Retina and Optic Nerve

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Abstract

S100B is a glial protein, which belongs to calcium-binding protein family. Alterations of S100B level were noted in various neurodegenerative diseases. In a new glaucoma-like animal model S100B was injected intravitreally, which led to neuronal degeneration in retina and optic nerve. The pathological mechanisms are still unknown. Therefore, S100B protein was intravitreally injected in rats. At days 14 and 21, retina, optic nerve, serum, and aqueous humor were investigated. S100B injection led to an increase of retinal NF-κB at day 14. Furthermore, higher IL-1β levels in retina, serum, and aqueous humor were measured. A co-localization of microglia and IL-1β was noted, which correlated with an increased microglia response in retina and optic nerve at day 14. At the same point in time, more apoptotic RGCs and a decline in RGC numbers were observed. At 21 days, this damage was still present, but no signal pathway activations were detectable anymore. Interestingly, macroglia were not affected at any point in time. We conclude that S100B activated the NF-κB signal pathway, which then regulated IL-1β production and release from microglia. A positive feedback loop of IL-1β likely stimulates microglia in a pro-inflammatory manner. These microglia probably induce apoptotic damage in retina and optic nerve. Meanwhile, the injected S100B protein was naturally degraded, which explains the resting state of the pro-inflammatory signal pathways with constant damage later on. The inhibition of S100B release or microglia response could potentially decrease the damage in degenerative diseases, like glaucoma.

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Funding

This project was funded in part by the Ernst und Berta Grimmke Stiftung.

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Author notes

  1. Pia Grotegut and Sandra Kuehn contributed equally to the work presented here and should therefore be regarded as equivalent authors.

Authors and Affiliations

  1. Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892, Bochum, Germany

    Pia Grotegut, Sandra Kuehn, Wilhelm Meißner, H. Burkhard Dick & Stephanie C. Joachim

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  1. Pia Grotegut
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  2. Sandra Kuehn
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  3. Wilhelm Meißner
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  4. H. Burkhard Dick
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  5. Stephanie C. Joachim
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Correspondence to Stephanie C. Joachim.

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This study was carried out in accordance with the recommendations of ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. The protocol was approved by the animal care committee of North Rhine-Westphalia in Germany (84-02.04.2013.A442).

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Grotegut, P., Kuehn, S., Meißner, W. et al. Intravitreal S100B Injection Triggers a Time-Dependent Microglia Response in a Pro-Inflammatory Manner in Retina and Optic Nerve. Mol Neurobiol 57, 1186–1202 (2020). https://doi.org/10.1007/s12035-019-01786-4

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