TY - JOUR PY - 2020// TI - Sex does not influence visual outcomes after blast-mediated traumatic brain injury but IL-1 pathway mutations confer partial rescue JO - Investigative ophthalmology and visual science A1 - Evans, Lucy P. A1 - Boehme, Nickolas A1 - Wu, Shu A1 - Burghardt, Elliot L. A1 - Akurathi, Abhigna A1 - Todd, Brittany P. A1 - Newell, Elizabeth A. A1 - Ferguson, Polly J. A1 - Mahajan, Vinit B. A1 - Dutca, Laura M. A1 - Harper, Matthew M. A1 - Bassuk, Alexander G. SP - e7 EP - e7 VL - 61 IS - 12 N2 - 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.
Language: en
LA - en SN - 0146-0404 UR - http://dx.doi.org/10.1167/iovs.61.12.7 ID - ref1 ER -