Impact-acceleration head injury results in optic neuropathy in the thirteen-lined ground squirrel.

Abstract

Traumatic brain injury (TBI) caused by rapid head acceleration produces visual impairments from damage to the optic nerve (ON), as well as widespread perturbations of the central visual system. Widely used mouse and rat models have limitations in translational relevance due to their nocturnal habits and rod-dominant retinas. In contrast, the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) is diurnal and possesses a cone-dominant retina with high retinal ganglion cell (RGC) density and an interlocking astrocyte pattern in the nerve fiber layer-an anatomical feature shared with primates and humans but not observed in other common rodent models. These similarities make the thirteen-lined ground squirrel uniquely suited for modeling the complex, diffuse pathophysiology of human closed-head TBI. Using a repetitive closed-head impact paradigm, we establish the thirteen-lined ground squirrel as a translational model of TBI. Repeated impacts induce long-term pathology, including abnormal seasonal weight regulation and persistent visual dysfunction. Longitudinal ophthalmic assessments reveal retinal thinning and significant reductions in RGC function. Histological analysis confirms dorsal RGC loss and late-stage changes in ON glia. Together, these findings demonstrate that the thirteen-lined ground squirrel recapitulates systemic, behavioral, and visual dysfunction following TBI, establishing it as a promising model for neurotrauma and vision loss.