A pig model for optogenetic laryngeal pacemaking

Introduction Bilateral laryngeal paresis results in fixed vocal cords and diminished air passage. Current treatment options have to take a loss of function and also electrical stimulation faces technical limitations. We were able to show direct optogenetic stimulation of skeletal muscle from transgenic mice, expressing the blue light-sensitive cation channel Channelrhodopsin 2 (ChR2) and that selective illumination of the posterior cricoarytenoid muscles (PCA) opens the vocal folds in explanted larynges.

Objectives We establish a pig model to explore the translational potential of optogenetic laryngeal pacemaking focusing on an efficient gene transfer to express ChR2. Furthermore, we develop implantable light devices.

Methods We injected adeno-associated viruses (AAV) expressing ChR2 in fusion to mCherry and explored 14 days later light stimulation in vivo as well as ChR2 expression by quantifying mCherry fluorescence. We established surgical procedures for optogenetic stimulation in vivo.

Results Using a diverticuloscope according to Weerda, we injected AAV into the postcricoid region. In final examination, we test light stimulation by transoral placement of light guides into the postcricoid region and record the glottis movement by videoscopy. Second, we perform a transcervical median pharyngotomy and luxate the larynx at the cranial part while maintaining blood supply. This functional readout revealed single twitches of the PCA and mCherry fluorescence confirming ChR2 expression.

Conclusion We established a pig model to study the translational potential of optogenetic laryngeal pacemaking, including local gene transfer. First experiments revealed muscle-specific expression of ChR2 leading to single twitch of PCA-fibers.

Poster-PDF A-1143.pdf

Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 413501650; 452139556

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Artikel online veröffentlicht:
13. Mai 2021