| Autor: |
F Knapman, M Cohen, T Kulaga, L Lisowski, N Lovell, S McMullan, P Burke, L Bilston |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
SLEEP Advances. 3:A1-A1 |
| ISSN: |
2632-5012 |
| DOI: |
10.1093/sleepadvances/zpac029.001 |
| Popis: |
INTRODUCTION Many obstructive sleep apnea (OSA) patients are sub-optimally treated due to poor tolerance or incomplete response to established therapies. We propose a novel stimulation therapy that sensitises the dilator muscles to light activation (‘optogenetics') and activates the muscles with light during sleep. This study aims to determine feasibility in a rodent model of OSA and identify effective optogenetic constructs. METHODS Rats received intramuscular injections of a viral vector encapsulating the opsin ChR2, driven by either a muscle-specific or non-specific promotor. Three weeks post-injection, opsin expression was quantified via confocal imaging. Light-induced tongue muscle activity afforded by the superior promotor was then measured in an acute model of OSA. The superior promotor was then combined with a novel muscle-targeted viral vector and, light-induced airway dilation was measured with ultrasound imaging. RESULTS With the muscle-specific promotor, opsin expression in the tongue was 470%(p=0.013, RM-ANOVA) greater, and brainstem expression was abolished. In the animals who received this superior promotor, light stimulation facilitated a 56% increase in muscle activity from that recorded during unstimulated breaths in an acute model of OSA(p DISCUSSION The combined muscle-specific promotor and muscle-specific viral vector resulted in a novel and highly effective method of inducing light-sensitivity in upper airway muscles and facilitating light-induced airway dilation. This study provides proof-of-concept for a non-invasive optogenetics-based OSA therapy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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