Sex Does Not Influence Visual Outcomes After Blast-Mediated Traumatic Brain Injury but IL-1 Pathway Mutations Confer Partial Rescue

Lucy P Evans; Nickolas Boehme; Shu Wu; Elliot L Burghardt; Abhigna Akurathi; Brittany P Todd; Elizabeth A Newell; Polly J Ferguson; Vinit B Mahajan; Laura M Dutca; Matthew M Harper; Alexander G Bassuk

doi:10.1167/iovs.61.12.7

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Sex Does Not Influence Visual Outcomes After Blast-Mediated Traumatic Brain Injury but IL-1 Pathway Mutations Confer Partial Rescue

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Sex Does Not Influence Visual Outcomes After Blast-Mediated Traumatic Brain Injury but IL-1 Pathway Mutations Confer Partial Rescue

Lucy P Evans, Nickolas Boehme, Shu Wu, Elliot L Burghardt, Abhigna Akurathi, Brittany P Todd, Elizabeth A Newell, Polly J Ferguson, Vinit B Mahajan, Laura M Dutca, …

Investigative ophthalmology & visual science, Vol.61(12), pp.7-7

10/01/2020

DOI: 10.1167/iovs.61.12.7

PMCID: PMC7582458

PMID: 33030508

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Abstract

In a mouse model of blast-mediated traumatic brain injury (bTBI), interleukin-1 (IL-1)-pathway components were tested as potential therapeutic targets for bTBI-mediated retinal ganglion cell (RGC) dysfunction. Sex was also evaluated as a variable for RGC outcomes post-bTBI. Male and female mice with null mutations in genes encoding IL-1α, IL-1β, or IL-1RI were compared to C57BL/6J wild-type (WT) mice after exposure to three 20-psi blast waves given at an interblast interval of 1 hour or to mice receiving sham injury. To determine if genetic blockade of IL-1α, IL-1β, or IL-1RI could prevent damage to RGCs, the function and structure of these cells were evaluated by pattern electroretinogram and optical coherence tomography, respectively, 5 weeks following blast or sham exposure. RGC survival was also quantitatively assessed via immunohistochemical staining of BRN3A at the completion of the study. Our results showed that male and female WT mice had a similar response to blast-induced retinal injury. Generally, constitutive deletion of IL-1α, IL-1β, or IL-1RI did not provide full protection from the effects of bTBI on visual outcomes; however, injured WT mice had significantly worse visual outcomes compared to the injured genetic knockout mice. Sex does not affect RGC outcomes after bTBI. The genetic studies suggest that deletion of these IL-1 pathway components confers some protection, but global deletion from birth did not result in a complete rescue.

Details

Title: Subtitle: Sex Does Not Influence Visual Outcomes After Blast-Mediated Traumatic Brain Injury but IL-1 Pathway Mutations Confer Partial Rescue
Creators: Lucy P Evans - Medical Scientist Training Program, University of Iowa, Iowa City, Iowa, United States
Nickolas Boehme - Iowa City VA Health Care System Center for the Prevention and Treatment of Visual Loss, Iowa City, Iowa, United States
Shu Wu - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States
Elliot L Burghardt - Department of Biostatistics, University of Iowa, Iowa City, Iowa, United States
Abhigna Akurathi - Iowa City VA Health Care System Center for the Prevention and Treatment of Visual Loss, Iowa City, Iowa, United States
Brittany P Todd - Medical Scientist Training Program, University of Iowa, Iowa City, Iowa, United States
Elizabeth A Newell - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States
Polly J Ferguson - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States
Vinit B Mahajan - Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States
Laura M Dutca - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
Matthew M Harper - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
Alexander G Bassuk - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.61(12), pp.7-7
DOI: 10.1167/iovs.61.12.7
PMID: 33030508
PMCID: PMC7582458
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: P30 EY026877 / NEI NIH HHS R01 EY025225 / NEI NIH HHS I01 RX000952 / RRD VA R01 NS098590 / NINDS NIH HHS IK2 RX002003 / RRD VA R01 EY024698 / NEI NIH HHS F30 EY031245 / NEI NIH HHS T32 GM007337 / NIGMS NIH HHS R01 AR059703 / NIAMS NIH HHS R01 EY024665 / NEI NIH HHS R21 AG050437 / NIA NIH HHS
Language: English
Date published: 10/01/2020
Academic Unit: Neurology; 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: 9984070963502771

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