Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice

2022 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice​
Bali, B.; Gruber-Dujardin, E.; Kusch, K. ; Rankovic, V.   & Moser, T. ​ (2022) 
Life Science Alliance5(8) art. e202101338​.​ DOI: https://doi.org/10.26508/lsa.202101338 

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Authors
Bali, Burak; Gruber-Dujardin, Eva; Kusch, Kathrin ; Rankovic, Vladan ; Moser, Tobias 
Abstract
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.
Issue Date
2022
Journal
Life Science Alliance 
Project
EXC 2067: Multiscale Bioimaging 
Working Group
RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding) 
External URL
https://mbexc.uni-goettingen.de/literature/publications/481
eISSN
2575-1077
Language
English
Sponsor
European Research Council
Deutsche Forschungsgemeinschaft
Fondation Pour l’Audition
Deutsche Forschungsgemeinschaft

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