Gene Therapy Restores Auditory Functions in an Adult Vglut3 Knockout Mouse Model.

Adeno-associated virus (AAV)-based gene therapy has been demonstrated to be extremely effective for treating genetic hearing loss over the past several years. However, successful gene therapies for hereditary deafness have not been well-studied in adult mice. To explore the possibility of gene therapy after peripheral auditory maturity, we used AAV8 to express vesicular glutamate transporter 3 (Vglut3) in the cochleae of 5w, 8w, and 20w Vglut3KO mice. Results indicated that AAV8-Vglut3 could mediate the exogenous expression of Vglut3 in all inner hair cells (IHCs). Auditory function was successfully restored, and the hearing threshold remained stable for at least 12 weeks after rescue. Moreover, the results revealed that the number of synaptic ribbons, as well as their morphology, was significantly recovered after gene therapy, potentially indicating the glutamate-dependent plasticity of IHCs. Taken together, our data introduce the possibility of gene therapy in adult mice and advance our knowledge of the role of Vglut3 in presynaptic plasticity.