Journal Article

Torsion-Induced Traumatic Optic Neuropathy (TITON): A physiologically relevant animal model of traumatic optic neuropathy

Rodriguez, Luis, Sponsel, William E., Racine, Julie, Ryan, Annie K., Glickman, Randolph D., Reilly, Matthew A., Rex, Tonia S., Asemota, Brooke I., Heisler-Taylor, Tyler, Mello, Claire

2025

Overview

Traumatic optic neuropathy (TON) is a common cause of irreversible blindness following head injury. TON is characterized by axon damage in the optic nerve followed by retinal ganglion cell death in the days and weeks following injury. At present, no therapeutic or surgical approach has been found to offer any benefit beyond observation alone. This is due in part to the lack of translational animal models suitable for understanding mechanisms and evaluating candidate treatments. In this study, we developed a rat model of TON in which the eye is rapidly rotated, inflicting mechanical stress on the optic nerve and leading to significant visual deficits. These functional deficits were thoroughly characterized up to one week after injury using electrophysiology and immunohistochemistry. The photopic negative response (PhNR) of the light adapted full field electroretinogram (LA ffERG) was significantly altered following injury. This correlated with increased biomarkers of retinal stress, axon disruption, and cell death. Together, this evidence suggests the utility of our model for mimicking clinically relevant TON and that the PhNR may be an early diagnostic for TON. Future studies will utilize this animal model for evaluation of candidate treatments.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adaptation / Anesthesia / Animal models / Animal models in research / Animals / Axons - pathology / Biology and Life Sciences / Biomarkers / Cell culture / Cell death / Disease Models, Animal / Electrophysiology / Electroretinography / Eye / Head injuries / Immunohistochemistry / Injuries / Laboratories / Male / Medicine and Health Sciences / Motion control / Nerves / Optic nerve / Optic Nerve - pathology / Optic Nerve - physiopathology / Optic Nerve Injuries - etiology / Optic Nerve Injuries - pathology / Optic Nerve Injuries - physiopathology / Optic neuropathy / Physical Sciences / Pilot projects / Rats / Rats, Sprague-Dawley / Retina / Retina - pathology / Retina - physiopathology / Retinal Ganglion Cells - pathology / Social Sciences / Steroids / Trauma / Traumatic brain injury / Visual observation