PT  - JOURNAL ARTICLE
AU  - Burak Bali
AU  - Eva Gruber-Dujardin
AU  - Kathrin Kusch
AU  - Vladan Rankovic
AU  - Tobias Moser
TI  - Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice
AID  - 10.26508/lsa.202101338
DP  - 2022 Aug 01
TA  - Life Science Alliance
PG  - e202101338
VI  - 5
IP  - 8
4099  - https://www.life-science-alliance.org/content/5/8/e202101338.short
4100  - https://www.life-science-alliance.org/content/5/8/e202101338.full
SO  - Life Sci. Alliance2022 Aug 01; 5
AB  - AAV-mediated optogenetic neural stimulation has become a clinical approach for restoring function in sensory disorders and feasibility for hearing restoration has been indicated in rodents. Nonetheless, long-term stability and safety of AAV-mediated channelrhodopsin (ChR) expression in spiral ganglion neurons (SGNs) remained to be addressed. Here, we used longitudinal studies on mice subjected to early postnatal administration of AAV2/6 carrying fast gating ChR f-Chrimson under the control of the human synapsin promoter unilaterally to the cochlea. f-Chrimson expression in SGNs in both ears and the brain was probed in animals aged 1 mo to 2 yr. f-Chrimson was observed in SGNs at all ages indicating longevity of ChR-expression. SGN numbers in the AAV-injected cochleae declined with age faster than in controls. Investigations were extended to the brain in which viral transduction was observed across the organ at varying degrees irrespective of age without observing viral spread-related pathologies. No viral DNA or virus-related histopathological findings in visceral organs were encountered. In summary, our study demonstrates life-long (24 mo in mice) expression of f-Chrimson in SGNs upon single AAV-dosing of the cochlea.