June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
An Electrophysiological Technique for the Diagnosis of TON in a Small Animal Model
Author Affiliations & Notes
  • Annie Kathleen Ryan
    Biomedical Engineering, The Ohio State University, Columbus, Ohio, United States
  • Claire Landreth
    Visual Sciences, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Rachael Cheung
    Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Elisabeth Artis
    Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Tonia S Rex
    Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Julie Racine
    Department of Ophthalmology, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Matthew A. Reilly
    Biomedical Engineering, The Ohio State University, Columbus, Ohio, United States
  • Footnotes
    Commercial Relationships   Annie Ryan None; Claire Landreth None; Rachael Cheung None; Elisabeth Artis None; Tonia Rex None; Julie Racine None; Matthew Reilly None
  • Footnotes
    Support  US Department of Defense Vision Research Program Award W81XWH-15-1-0074
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5213. doi:
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      Annie Kathleen Ryan, Claire Landreth, Rachael Cheung, Elisabeth Artis, Tonia S Rex, Julie Racine, Matthew A. Reilly; An Electrophysiological Technique for the Diagnosis of TON in a Small Animal Model. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5213.

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

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Abstract

Purpose : Traumatic optic neuropathy (TON) is a frequent, vision-threatening complication of head injury. TON is incredibly difficult to diagnose before irreversible vision loss occurs. There are no effective treatments and translational animal models are limited. Electroretinograms (ERGs) allow objective determination of functional loss in the retina and optic nerve after TON. The purpose of this study was to develop functional electrophysiologic diagnostic criteria in a small animal model to allow future characterization of treatment safety and efficacy.

Methods : Male Sprague Dawley rats (~200grams) were utilized (n=6), and all animal work was performed with IACUC approval. Light-adapted ERGs including Photopic Negative Responses (PhNRs) were conducted before injury (Baseline), 24 hours after injury (D1), and 7 days after injury (D7) to assess retinal function in an animal model of torsional TON. After ERGs, animals were sacrificed, and retinal and optic nerve tissues were collected for structural analysis. The right eyes were injured utilizing a custom torsional injury-inducing device on D0. The left eyes did not receive the injury event. All ERG signals were compared to determine statistical differences in amplitudes and peak times at different time points and between eyes.

Results : Statistically significant differences were detected between the right eye at D1 and the right eye at D7 for the PhNR waveform amplitude. No statistically significant differences were determined for any of the other ERG waveforms amplitudes or for any of the peak times. Epifluorescence micrographs of optic nerve segments depicted significant reductions in both β-tubulin and GFAP labeling in the injured eyes.

Conclusions : Our results suggest the amplitude of the PhNR may provide early diagnostic information in TON. Based on our observed PhNR amplitudes we conclude our injury is altering the functionality of the RGCs and their axons. Further, the reductions in epifluorescence of β-tubulin in the injured eye optic nerves suggests a deficit in the number of microtubules within each axon, which points towards a loss of axons in the injured eyes. The significant reduction in epifluorescence of β-tubulin in conjunction with the significantly altered PhNR amplitudes supports our model and that torsionally induced TON can cause a detectable injury. Therefore, the PhNR may be beneficial towards the early diagnosis of TON.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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