September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A Novel Animal Model for Traumatic Optic Neuropathy (TON)
Author Affiliations & Notes
  • Wensi Tao
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States
  • Brian Tse
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States
  • Galina Dvoriantchikova
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States
  • Dmitry V Ivanov
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States
  • David T Tse
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States
  • Daniel Pelaez
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States
  • Footnotes
    Commercial Relationships   Wensi Tao, None; Brian Tse, None; Galina Dvoriantchikova, None; Dmitry Ivanov, None; David Tse, None; Daniel Pelaez, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5090. doi:
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      Wensi Tao, Brian Tse, Galina Dvoriantchikova, Dmitry V Ivanov, David T Tse, Daniel Pelaez; A Novel Animal Model for Traumatic Optic Neuropathy (TON). Invest. Ophthalmol. Vis. Sci. 2016;57(12):5090.

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

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Abstract

Purpose : Traumatic optic neuropathy (TON) is a devastating cause of permanent visual loss following blunt injury to the head. The indirect injury occurs as a concussive force to the orbit is transmitted at a distance through the skull to the optic nerve. Several animal models have been used to simulate TON– all of which can produce similar end-results of retinal ganglion cell(RGC) loss, but fail to reproduce the clinical scenario of closed head indirect injury to the nerve and subsequent neurodegeneration. Thus, we developed a clinically-relevant animal model for TON using a novel ultrasonic pulse injury modality.

Methods : To trigger Traumatic Optic Neuropathy (TON), 3 month-old C57BL/6 mice were anesthetized, and a microtip probe (3 mm) of a laboratory sonifier was placed on the supraorbital border directly above the insertion of the optic nerve into the optic canal. A 500 msec ultrasonic pulse at 35% amplitude (80J) was then delivered to the orbit. After the injury, mice were followed for up to 1 month and assessed for development of optic neuropathy. Whole retina flat-mounts were stained for retinal ganglion cell (RGC) quantification, optic nerves were harvested for immunohistochemistry and real-time PCR was performed. Nerve fiber layer thickness was measured by Spectral Domain Optical Coherence Tomography (SD-OCT). RGC function were assessed by pattern electroretinogram (pERG).

Results : The number of RGCs in the retina steadily decreased over a 2 week period with significant loss of RGCs in the injured retinas after 1 week. In the optic nerve, we found RNA and immunohistochemical expression of inflammatory markers such as TNF-alpha as early as 6 hours after injury. Immunohistochemistry showed activation of microglia (Cd11b) and infiltration of CD45-positive macrophages in the optic nerve and initiation of a gliotic response. One month after the injury, the RGC function measured by pERG was decreased significantly by 19.3% over baseline and the contralateral eye.

Conclusions : This ultrasonic pulse delivery method is capable of delivering a non-invasive concussive injury to the optic nerve and induce unilateral TON. Our results suggest that the traumatic event initiates a cascading sequence of metabolic events that can exacerbate the injury, and accounts for the progressive nature of neurodegeneration seen in the human manifestation. After the injury, we observed a decrease of RGC survival and function with an intact tissue ultrastructure.

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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