Abstract
Purpose :
Traumatic optic neuropathy (TON) is a frequent, vision-threatening complication of head injury. No treatments are currently available and translational animal models are limited. The purpose of this study was to develop functional electrophysiologic diagnostic criteria for using a small animal model.
Methods :
Male Sprague Dawley rats (~200g) were utilized, and all animal work was performed with IACUC approval. A series of light-adapted ERGs were conducted including flash ERGs (fERGs), flash Visual Evoked Potentials (fVEPs), and Photopic Negative Responses (PhNRs). ERG tests were conducted at least 7 days before injury (baseline), and 24 hours after injury (D1) to assess deterioration of visual function associated with the torsional TON. Rats were anesthetized with an intraperitoneal injection of ketamine/xylazine for each ERG session, and for the injury event (D0). All animals received baseline and D1 ERGs before sacrifice and tissue collection. The right eyes of all animals were injured utilizing a custom torsional injury-inducing device on D0. The left eyes of all animals remained uninjured. ERG signals were compared from baseline to D1 to determine differences in amplitudes and latencies at different time points.
Results :
There was a reduction in the right eye amplitudes in fERG b-waves, fVEPs, and PhNRs at D1 as compared to baseline values. The left eye amplitudes at D1 were not significantly different to the left eye baseline amplitudes for fERG b-waves, and PhNRs. However, fVEP amplitudes were significantly different from baseline. Higher b-wave amplitudes in the ERG signal were observed in the left eye at D1 as compared to the right eye amplitude at D1.
Conclusions :
A promising diagnostic technique for evaluation of the retina and visual system 24 hours after TON injury in a rat model. Comparing ERG and PhNR amplitudes between the ipsilateral and contralateral eyes may be a diagnostic for TON. Our small animal model detects the presence of visual system damage shortly after injury, which could allow for a promising diagnostic for humans in the future. Utilization of the differential amplitude between eyes may allow for diagnosis in humans where baselines are unavailable. Future work will evaluate changes at shorter time points and utilize these approaches to evaluate the safety and efficacy of candidate therapeutics for TON.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.