Ocular blast trauma induces multiple pathological changes in the retina and optic nerve that can result in permanent vision loss. Previous research has focused on characterizing various models of whole body or head blast injury in rodents. We characterized the response of ocular blast injury in three genetically distinct inbred strains of mice (C57Bl/6J, DBA/2J and Balb/cJ) to determine if genetic susceptibility played a role in the pathogenesis. The DBA/2J and Balb/cJ mouse strains were the most susceptible to ocular blast injury, so we used these strains to test the efficacy of erythropoietin (EPO), a neuroprotective cytokine, as a therapeutic agent for ocular blast injury. EPO either protected against or exacerbated the injury, which was dependent upon treatment timing. We found that early treatment with EPO elevated retinal iron levels and likely caused increased oxidative stress through the Fenton reaction. Additionally, we assessed the role of oxidative stress in ocular blast injury using the Gulo-/- mouse, which lacks the enzyme necessary for vitamin C synthesis and exhibits increased oxidative stress in neuronal tissue. The Gulo-/- mouse exhibited a similar injury phenotype to the control strain, the C57B/6J. This may be due to vitamin Câs inability to effectively prevent peroxynitrite formation, a potential key mediator of the pathogenesis of ocular blast injury.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-11192016-195913 |
| Date | 23 November 2016 |
| Creators | Bricker-Anthony, Courtney Michelle |
| Contributors | David J. Calkins, Ph.D., Rebecca M. Sappington, Ph.D., Tonia S. Rex, Ph.D., Kevin L. Schey, Ph.D. |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-11192016-195913/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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