Human retinal organoids functionally bridge a transected optic nerve in a rat model.

Abstract

Functional restoration of vision in adult mammals remains unattainable following complete transection of the optic nerve. In this study, we address this challenge by heterotopically transplanting human retinal organoids into the transection cavity of the optic nerve in adult rats. One month after transplantation, treated animals exhibited partial recovery of visual function, including a direct pupillary light reflex, visually evoked electrophysiological responses, and visually guided behaviors, which were sustained for at least 3 months. Neuroanatomical tracing and three-dimensional imaging revealed the formation of a structured host-graft coupling spanning the transection gap. Functional engagement of the graft was further supported by chemogenetic inhibition, which led to coordinated attenuation of visual function. Together, these findings provide proof of concept that heterotopic retinal organoid transplantation can establish a relay-like pathway supporting partial functional signal transmission across a completely transected optic nerve, offering an alternative conceptual framework for repairing severe optic nerve injuries.