bioRxiv2019
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, with an interblast 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 lL-1{beta}, IL-1, IL-6, and TNF 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. Inhibition of the IL-1 pathway was accomplished using anakina, an IL-1RI antagonist. Retinal function and structure 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 tred of decreased 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.\n\nSignificance StatementBlast-mediated traumatic brain injury (bTBI) affects military members and civilians as a direct result of combat, workplace accidents, or intentional terrorist attacks. The retina is a central nervous system (CNS) tissue that is vulnerable to blast exposure. Individuals with bTBI often report visual dysfunction, but the mechanisms of ocular injury are poorly understood. This study demonstrates that damaging neuroinflammation contributes to retinal injury following blast-mediated TBI. We also identified anakinra, an anti-IL-1 therapy currently utilized for other diseases, as a potential pharmacologic agent that could prevent ocular damage after blast. These findings will aide in the development of novel treatments for vision preservation.