P063 Optogenetics for Obstructive Sleep Apnea

INTRODUCTION: We propose a novel sleep apnea therapy whereby a viral vector construct induces opsin expression and therefore light sensitivity to the upper airway muscles. Pulsed light to these muscles during sleep will enhance muscle contractions resulting in airway dilation and apnea prevention. Here we investigate the therapy’s feasibility, and determine whether a muscle-specific promotor induces superior expression and light-evoked EMG responses compared to a non-specific promotor. Superiority will be determined by the strength and specificity of opsin expression as restricting expression to the tongue minimises the likelihood of immune responses and unwanted sensation, movement or pain with light application. METHODS: 10 rats received an intramuscular injection of a viral vector construct to induce opsin expression in the tongue. 4 rats received a non-specific construct and 6 received a muscle-specific construct. Pulsed light was applied directly to the tongue, and genioglossus EMG activity was recorded. Confocal imaging of the brainstem and tongue quantified the strength and specificity of opsin expression. RESULTS: Despite the greater titer of the non-specific construct, the muscle-specific construct consistently drove stronger expression in the tongue and subsequently greater light-evoked EMG activity. Additionally, whilst the non-specific construct drove retrograde gene expression in hypoglossal motor neurons, no retrograde expression was induced by the muscle-specific construct. CONCLUSIONS: This study provides proof-of-concept of a non-invasive optogenetic stimulation-based therapy for OSA. The superior expression and light induced EMG activity generated by the muscle-specific promotor indicates that it is the preferred promotor for future studies employing direct optogenetic stimulation of skeletal muscle.