Differential resilience against complete optic nerve transection across visual areas.

Understanding how the central visual system responds to complete optic nerve transection (ONT) is critical for evaluating the feasibility of whole-eye transplantation (WET), as envisioned by the 2024 ARPA-H THETA program. This study evaluates the dynamitic neuronal and synaptic changes within the posterior visual pathway-the superior colliculus (SC), lateral geniculate nucleus (LGN), and primary visual cortex (V1)-after optic nerve crush (ONC) and ONT in mice models. Complementary observations were obtained in non-human primates. Both injury models induced time-dependent alterations, but degeneration severity differed across brain regions. The SC and LGN exhibited preserved neuronal and synaptic densities, indicating strong structural resilience. On the contrary, V1 displayed early and sustained neuronal and synaptic loss. These findings suggest that the posterior visual pathway maintains a prolonged structural window that could enable long-distance optic nerve regeneration and eye-brain reconnection.