September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Protection from blast-induced vision loss by the N-acetylserotonin derivative HIOC through a BDNF/TrkB receptor mechanism
Author Affiliations & Notes
  • P. Michael Iuvone
    Ophthalmology, Emory University Sch of Med, Atlanta, Georgia, United States
    Pharmacology, Emory University Sch of Med, Atlanta, Georgia, United States
  • Polina Lyuboslavsky
    Ophthalmology, Emory University Sch of Med, Atlanta, Georgia, United States
  • Curran Sidhu
    Ophthalmology, Emory University Sch of Med, Atlanta, Georgia, United States
  • Li He
    Ophthalmology, Emory University Sch of Med, Atlanta, Georgia, United States
  • Jeffrey H Boatright
    Ophthalmology, Emory University Sch of Med, Atlanta, Georgia, United States
  • Eldon E Geisert
    Ophthalmology, Emory University Sch of Med, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   P. Michael Iuvone, None; Polina Lyuboslavsky, None; Curran Sidhu, None; Li He, None; Jeffrey Boatright, None; Eldon Geisert, None
  • Footnotes
    Support  DoD CDMRP Grants W81XWH-12-1-0436, W81XWH1210255; NIH P30EY006360; Research to Prevent Blindness; The Abraham and Phyllis Katz Foundation
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 737. doi:
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      P. Michael Iuvone, Polina Lyuboslavsky, Curran Sidhu, Li He, Jeffrey H Boatright, Eldon E Geisert; Protection from blast-induced vision loss by the N-acetylserotonin derivative HIOC through a BDNF/TrkB receptor mechanism. Invest. Ophthalmol. Vis. Sci. 2016;57(12):737.

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

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Abstract

Purpose : N-Acetylserotonin activates BDNF/TrkB receptors but its biological half-life following systemic injection is short and not therapeutically beneficial. The present study examines the neuroprotective effects of HIOC, a structural analog of N-acetylserotonin with a longer half-life, in preserving visual function after blast injury to the eye.

Methods : Mice were exposed to a single ~48psi blast directed at the eye using the method of Hines-Beard et al. (Exp Eye Res 2012;99:63-70). They were injected with vehicle or HIOC (40mg/kg, intraperitineally) 30 min before, or 0.25hr, 1hr, 3hr, or 24hr after exposure to blast. Injections continued daily for 6 days. Contrast sensitivity and visual acuity were measured 1 week, 1 month, and 4 months after exposure to blast by optokinetic tracking. Optic nerve axon counts were made 4 months after blast exposure in mice treated initially 15 min after blast. To test the role of BDNF/TrkB receptors, mice were treated with ANA-12, a selective TrkB antagonist (Cazorla et al., J Clin Invest 2011;121:1846-1857), 2.5 hr before each HIOC or vehicle injection.

Results : One week after blast, contrast sensitivity (p<0.001), but not visual acuity, was significantly reduced in vehicle treated mice compared to naïve controls that were not exposed to blast. At 1 and 4 months after blast, both contrast sensitivity (p<0.001) and visual acuity (p<0.001) were reduced compared to naïve controls. In mice initially treated with HIOC 30 min before or 0.25hr, 1hr, or 3hr after blast, contrast sensitivity and visual acuity were significantly better than vehicle-treated mice (p<0.001), and not significantly different than naïve controls. If the initial treatment with HIOC was delayed by 24hr after blast, the protective effect on visual function was not observed. Four months after exposure to blast, axon numbers in the optic nerve were significantly reduced in vehicle-treated mice (p<0.001), but not in HIOC treated mice. Pretreatment with ANA-12 completely blocked the protective effect of HIOC against blast-induced vision loss.

Conclusions : HIOC preserves vision in mice exposed to blast if the initial treatment is within a critical period (<3hr). Treatment with HIOC for 1 week preserves visual function for at least 4 months. The effect of HIOC is mediated by activation of BDNF/TrkB receptors.

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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