Modulation of post-traumatic immune response using the IL-1 receptor antagonist anakinra for improved visual outcomes.

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ID: 95892
2020
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Abstract
The purpose of this study was to characterize acute changes in inflammatory pathways in the mouse eye following a blast-mediated TBI (bTBI) model, and to determine if modulation of these pathways could protect the structure and function of retinal ganglion cells (RGC). bTBI was induced in C57BL/6J male mice by exposure to three 20 PSI blast waves directed towards the head with the body shielded, with an inter-blast interval of one hour. Acute cytokine expression in retinal tissue was measured through real-time quantitative polymerase chain reaction (RT-qPCR) 4 hours post-blast. Increased retinal expression of IL-1α, IL-1β, IL-6, and TNFα was observed in bTBI mice exposed to blast when compared to shams, which was associated with activation of microglia and macroglia reactivity, assessed via immunohistochemistry with IBA-1 and GFAP, respectively, 1 week post-blast. Blockade of the IL-1 pathway was accomplished using anakinra, an IL-1RI antagonist, administered intraperitoneally for 1 week prior to injury and continuing for 3 weeks post-injury. Retinal function and RGC layer thickness were evaluated 4 weeks post-injury using pattern electroretinogram (PERG) and optical coherence tomography (OCT), respectively. After bTBI, anakinra treatment resulted in a preservation of RGC function and RGC structure when compared to saline treated bTBI mice. Optic nerve integrity analysis demonstrated a trend of decreased damage suggesting that IL-1 blockade also prevents axonal damage after blast. Blast exposure results in increased retinal inflammation including upregulation of pro-inflammatory cytokines and activation of resident microglia and macroglia. This may partially explain the RGC loss we observed in this model as blockade of the acute inflammatory response after injury with the IL-1R1 antagonist anakinra resulted in preservation of RGC function and structure. Key Words: Blast; IL-1; anakinra; retina; visual function.
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evans2020modulationjournal Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Evans, Lucy P;Woll, Addison W;Wu, Shu;Todd, Brittany P;Hehr, Nicole N;Hedberg-Buenz, Adam;Anderson, Michael G;Newell, Elizabeth A;Ferguson, Polly J;Mahajan, Vinit B;Harper, Matthew M;Bassuk, Alexander G;
Journal journal of neurotrauma
Year 2020
DOI
10.1089/neu.2019.6725
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