June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Development of an acoustic-driven model of traumatic brain injury (TBI) in order to measure changes in the zebrafish retina and central visual pathways
Author Affiliations & Notes
  • Salvatore L Stella
    Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania, United States
  • Dillon McDevitt
    Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania, United States
  • Lance Sommer
    Neurology, Penn State University College of Medicine, Hershey, Pennsylvania, United States
  • Yunsung Kim
    Neurology, Penn State University College of Medicine, Hershey, Pennsylvania, United States
  • Mark Stahl
    Neurology, Penn State University College of Medicine, Hershey, Pennsylvania, United States
    Neural and Behavioral Sciences, Penn State University College of Medicine, Hershey, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Salvatore Stella, None; Dillon McDevitt, None; Lance Sommer, None; Yunsung Kim, None; Mark Stahl, None
  • Footnotes
    Support  H. G. Barsumian, M.D. Memorial Fund and George L. Laverty Foundation.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5872. doi:
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      Salvatore L Stella, Dillon McDevitt, Lance Sommer, Yunsung Kim, Mark Stahl; Development of an acoustic-driven model of traumatic brain injury (TBI) in order to measure changes in the zebrafish retina and central visual pathways. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5872.

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

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Abstract

Purpose : The retina serves as a window into the brain and this conduit is comprised of retinal ganglion cell axons, which combine to form the optic nerve and central visual pathways. Vision loss following head trauma, affects 20-40% of all people who suffer brain injuries. The causes of post-traumatic vision loss are varied and include direct ocular, nerve, or brain injury, but the mechanisms behind this neurodegeneration are unknown. Animal models are needed that can recapitulate the pathological cascade of human TBI. The aim of this study is to develop a novel vertebrate model of TBI in zebrafish in which multiple biological readouts can be evaluated.

Methods : TBI was elcited in zebrafish following anesthesia with MS-222, and placed in a mesh inside a tank above an underwater speaker. An acostic mass was delived in the form of sound pressure via the speaker to the zebrafish. Visual behavior to light and swimming reflexes were analyzed in both larvae and adults using a Zebrabox. Structural changes were mapped with a pan neuronal marker (elav) driven by GFP or with immunohistochemical detection of phosphorylated ERK as a readout of neural activity in the retina and brain. Western blots and immunohistochemistry were used to measure chronic traumatic encephalopathy (e.g., tau, TDP-43) to quantify changes in protein levels in the retina and brain.

Results : We found a significant decrease in locomotion ( p < 0.05) and mean velocity ( p < 0.05) following TBI treatment in both adults and larvae. GFP labeling of axons visualized damage to both visual and non-visual targets in the zebrafish brain. p-ERK labeling showed a loss of neuronal activity in TBI treated zebrafish. Our results also indicate that significant changes occur in proteins related to chronic traumatic encephalopathy in both the retina and the brain (tau and TDP-43).

Conclusions : Taken together, this novel form of acoustic generated TBI in zebrafish has the potential to be applied to both larval and adult zebrafish as a viable model that can recapitulate TBI damage in humans. This approach provides a stepping stone and tool for deciphering the long term visual changes that occur in both the retina and the brain following TBI.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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