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Title page for ETD etd-11192016-195913


Type of Document Dissertation
Author Bricker-Anthony, Courtney Michelle
Author's Email Address cmbricker21@gmail.com
URN etd-11192016-195913
Title Ocular Blast Trauma: Mechanisms of Degeneration and a Potential Therapeutic Strategy
Degree PhD
Department Neuroscience
Advisory Committee
Advisor Name Title
David J. Calkins, Ph.D. Committee Chair
Kevin L. Schey, Ph.D. Committee Member
Rebecca M. Sappington, Ph.D. Committee Member
Tonia S. Rex, Ph.D. Committee Member
Keywords
  • oxidative stress
  • erythropoietin
  • ocular trauma
  • blast injury
Date of Defense 2016-08-30
Availability unrestricted
Abstract
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 C’s inability to effectively prevent peroxynitrite formation, a potential key mediator of the pathogenesis of ocular blast injury.
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