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Ying Li, Rebecca King, Felix L Struebing, P. Michael Iuvone, Eldon E Geisert; Activation of the immune system following blast injury to the eye. Invest. Ophthalmol. Vis. Sci. 2016;57(12):739. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Our group at Emory is characterizing the effects of a 48psi blast injury to the eye. The present study examines the activation of the innate immune system and the chronic infiltration of T-cells into the compromised retina.
Blast injury was produced using a modified paintball gun (Hines-Beard et al. Exp. Eye Res 2012, 99:36-41) in the BXD recombinant inbred (RI) strain set. Expression datasets were generated 5 days after blast and compared with normal retinal microarray datasets respectively constructed from 30 mouse strains. The dataset is presented on GeneNetwork (genenetwork.org). To further examine the activation of the innate immune system and the infiltration of T-cells, retinal whole mounts and sections of retina from control animals and retinas that had received a 48psi blast were examined using immunohistochemical methods.
The innate immune network and microglia are activated following blast with significant upregulation of C4b (p=0.01), Cx3cr1 (p=0.067), and Il-10 (p<0.001). In addition there is a clear indication that T-cells are invading the retina by the upregulation of CD4, FoxP3 and CD8 (known markers of lymphocyte subtypes). To investigate the possibility that lymphocytes were invading the retina, we examined a blast eye 10, 21 and 30 days following the initial injury. Surprisingly, we found a significant number of invading CD4, FOXP3 and CD8 positive T-cells. In addition, treating the animals for 1 week with Meloxicam (modulating the inflammatory response) or with Fingolimod (decreasing the invasions of lymphocytes) caused a significant increase in contrast sensitivity as measured by an optokinetic tracking system.
Following a 48psi blast injury to the mouse eye, the innate immune system is activated and subsequently T-cells invade the retina. These potentially deleterious events may be countered by treatments with FDA approved drugs. Currently we are examining the timing and effectiveness of potential therapeutics.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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