Modulation of Post-Traumatic Immune Response Using the IL-1 Receptor Antagonist Anakinra for Improved Visual Outcomes

Lucy P Evans; Addison W Woll; Shu Wu; Brittany P Todd; Nicole Hehr; Adam Hedberg-Buenz; Michael G Anderson; Elizabeth A Newell; Polly J Ferguson; Vinit B Mahajan; Matthew M Harper; Alexander G Bassuk

doi:10.1089/neu.2019.6725

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Modulation of Post-Traumatic Immune Response Using the IL-1 Receptor Antagonist Anakinra for Improved Visual Outcomes

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Modulation of Post-Traumatic Immune Response Using the IL-1 Receptor Antagonist Anakinra for Improved Visual Outcomes

Lucy P Evans, Addison W Woll, Shu Wu, Brittany P Todd, Nicole Hehr, Adam Hedberg-Buenz, Michael G Anderson, Elizabeth A Newell, Polly J Ferguson, Vinit B Mahajan, …

Journal of neurotrauma, Vol.37(12), pp.1463-1480

06/15/2020

DOI: 10.1089/neu.2019.6725

PMID: 32056479

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Abstract

The purpose of this study was to characterize acute changes in inflammatory pathways in the mouse eye after blast-mediated traumatic brain injury (bTBI) and to determine whether modulation of these pathways could protect the structure and function of retinal ganglion cells (RGC). The bTBI was induced in C57BL/6J male mice by exposure to three 20 psi blast waves directed toward the head with the body shielded, with an inter-blast interval of one hour. Acute cytokine expression in retinal tissue was measured through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) four hours post-blast. Increased retinal expression of interleukin ( lL)-1β, IL-1α, IL-6, and tumor necrosis factor (TNF)α was observed in bTBI mice exposed to blast when compared with shams, which was associated with activation of microglia and macroglia reactivity, assessed via immunohistochemistry with ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein, respectively, one week post-blast. Blockade of the IL-1 pathway was accomplished using anakinra, an IL-1RI antagonist, administered intra-peritoneally for one week before injury and continuing for three weeks post-injury. Retinal function and RGC layer thickness were evaluated four 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 with 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 explain partially 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 RGC layer thickness.

anakinra

IL-1

retina

Original

blast

visual function

Details

Title: Subtitle: Modulation of Post-Traumatic Immune Response Using the IL-1 Receptor Antagonist Anakinra for Improved Visual Outcomes
Creators: Lucy P Evans - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Addison W Woll - Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA
Shu Wu - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Brittany P Todd - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Nicole Hehr - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Adam Hedberg-Buenz - The Iowa City Department of Veterans Affairs Center for the Prevention and Treatment of Visual Loss, Iowa City, Iowa, USA
Michael G Anderson - The Iowa City Department of Veterans Affairs Center for the Prevention and Treatment of Visual Loss, Iowa City, Iowa, USA
Elizabeth A Newell - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Polly J Ferguson - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Vinit B Mahajan - Omics Laboratory, Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA
Matthew M Harper - The Iowa City Department of Veterans Affairs Center for the Prevention and Treatment of Visual Loss, Iowa City, Iowa, USA
Alexander G Bassuk - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Journal of neurotrauma, Vol.37(12), pp.1463-1480
DOI: 10.1089/neu.2019.6725
PMID: 32056479
NLM abbreviation: J Neurotrauma
ISSN: 0897-7151
eISSN: 1557-9042
Publisher: Mary Ann Liebert, Inc., publishers
Language: English
Date published: 06/15/2020
Academic Unit: Neurology; Molecular Physiology and Biophysics; Critical Care; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biology; Rheumatology, Allergy, and Immunology; Neurology (Pediatrics); Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9984070871302771

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