June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Traumatic Blast-Induced Closed Globe Injury Reduces Visual Function and Retinal Ganglion Cells of Thy1-CFP mice: Mitigation by a Small Molecule TrkB Activator
Author Affiliations & Notes
  • Curran Sidhu
    Ophthalmology, Emory University School of Medicine, Atlanta, GA
  • Polina Lyuboslavsky
    Ophthalmology, Emory University School of Medicine, Atlanta, GA
  • Micah A Chrenek
    Ophthalmology, Emory University School of Medicine, Atlanta, GA
  • Felix L Struebing
    Ophthalmology, Emory University School of Medicine, Atlanta, GA
  • Jana T Sellers
    Ophthalmology, Emory University School of Medicine, Atlanta, GA
  • Noah A. Setterholm
    Chemistry, Emory University, Atlanta, GA
  • Frank E. McDonald
    Chemistry, Emory University, Atlanta, GA
  • Jeffrey H Boatright
    Ophthalmology, Emory University School of Medicine, Atlanta, GA
  • Eldon E Geisert
    Ophthalmology, Emory University School of Medicine, Atlanta, GA
  • P. Michael Iuvone
    Ophthalmology, Emory University School of Medicine, Atlanta, GA
  • Footnotes
    Commercial Relationships Curran Sidhu, None; Polina Lyuboslavsky, None; Micah Chrenek, None; Felix Struebing, None; Jana Sellers, None; Noah Setterholm, None; Frank McDonald, None; Jeffrey Boatright, None; Eldon Geisert, None; P. Michael Iuvone, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 6032. doi:https://doi.org/
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      Curran Sidhu, Polina Lyuboslavsky, Micah A Chrenek, Felix L Struebing, Jana T Sellers, Noah A. Setterholm, Frank E. McDonald, Jeffrey H Boatright, Eldon E Geisert, P. Michael Iuvone; Traumatic Blast-Induced Closed Globe Injury Reduces Visual Function and Retinal Ganglion Cells of Thy1-CFP mice: Mitigation by a Small Molecule TrkB Activator. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):6032. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Pressure waves due to explosions can damage the neurons of the eye and visual centers in the brain, leading to loss of vision. There are few treatments for such injuries that can be deployed rapidly to mitigate such damage. We hypothesize that activation of the Brain-Derived Neurotrophic Factor (BDNF) receptor TrkB will be useful for this purpose. Here we report initial testing of a putative TrkB agonist in a model of ocular blast injury.

Methods: Traumatic blast-induced ocular injury in mice was produced using a calibrated blast gun that delivers a single blast of ~48psi (range 47-50psi) directed at the front of the eye (Hines-Beard et al., Exp Eye Res. 2012;99:63-70). Transgenic Thy1-CFP (cyan fluorescent protein) mice on a C57BL/6 background were used, allowing us to quantify retinal ganglion cell (RGC) death at various intervals after blast injury by RGC cell counts and by CFP fluorescence measurements in retinal extracts. Retinal morphology, microglial activation, and reactive gliosis were assessed by standard histological and immunocytochemical techniques. Visual and retinal function were assessed by optokinetic tracking (OKT) and electroretinogram (ERG), respectively. Mice were injected with vehicle or N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC; 20 or 40 mg/kg ip) daily for 1 week beginning on the day of blast exposure.

Results: Seven days after exposure to blast, many RGCs were hyper-fluorescent and swollen. These changes were accompanied by an increase in Iba1-immunopositive microglia, suggestive of an inflammatory response to blast, and an increase in GFAP, indicative of reactive gliosis. Exposure to blast suppressed visual contrast sensitivity as early as 1 week (p<0.001) and suppression persisted for at least the first 7 weeks (p<0.001). Blast caused significant loss of RGCs (p=0.008). No decrease in ERG a-wave or b-wave amplitudes was seen after blast, suggesting that damage was primarily in the inner retina. Treatment with HIOC for 1 week significantly decreased the loss of visual function following blast injury at 1 week (p<0.001) and at 1 month (p<0.001).

Conclusions: Blast injury to the front of the eye results in inner retinal damage and loss of visual function. TrkB activators may be useful in mitigating loss of RGCs and visual function caused by closed-globe blast injury.

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