Diffuse traumatic axonal injury in the optic nerve does not elicit retinal ganglion cell loss.

Much of the morbidity after traumatic brain injury (TBI) is associated with traumatic axonal injury (TAI). Although most TAI studies focus on corpus callosum white matter, the visual system has received increased interest. To assess visual system TAI, we developed a mouse model of optic nerve TAI. It is unknown, however, whether this TAI causes retinal ganglion cell (RGC) death. To address this issue, YFP (yellow fluorescent protein)-16 transgenic mice were subjected to mild TBI and followed from 2 to 28 days. Neither TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive or cleaved caspase-3-immunoreactive RGCs were observed from 2 to 28 days after TBI. Quantification of immunoreactivity of Brn3a, an RGC marker, demonstrated no RGC loss; parallel electron microscopic analysis confirmed RGC viability. Persistent RGC survival was also consistent with the finding of reorganization in the proximal axonal segments after TAI, wherein microglia/macrophages remained inactive. In contrast, activated microglia/macrophages closely enveloped the distal disconnected, degenerating axonal segments at 7 to 28 days after injury, thereby confirming that this model consistently evoked TAI followed by disconnection. Collectively, these data provide novel insight into the evolving pathobiology associated with TAI that will form a foundation for future studies exploring TAI therapy and its downstream consequences.