|Title||Sex Does Not Influence Visual Outcomes After Blast-Mediated Traumatic Brain Injury but IL-1 Pathway Mutations Confer Partial Rescue.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Evans, Lucy P., Boehme Nickolas, Wu Shu, Burghardt Elliot L., Akurathi Abhigna, Todd Brittany P., Newell Elizabeth A., Ferguson Polly J., Mahajan Vinit B., Dutca Laura M., Harper Matthew M., and Bassuk Alexander G.|
|Journal||Invest Ophthalmol Vis Sci|
|Date Published||2020 Oct 01|
Purpose: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
|Alternate Journal||Invest Ophthalmol Vis Sci|
|PubMed Central ID||PMC7582458|
|Grant List||P30 EY026877 / EY / NEI NIH HHS / United States |
R01 EY024665 / EY / NEI NIH HHS / United States
R01 NS098590 / NS / NINDS NIH HHS / United States
R01 EY024698 / EY / NEI NIH HHS / United States
R01 EY025225 / EY / NEI NIH HHS / United States
R01 AR059703 / AR / NIAMS NIH HHS / United States
I01 RX000952 / RX / RRD VA / United States
IK2 RX002003 / RX / RRD VA / United States
R21 AG050437 / AG / NIA NIH HHS / United States
F30 EY031245 / EY / NEI NIH HHS / United States
T32 GM007337 / GM / NIGMS NIH HHS / United States