MOLECULAR BIOLOGICAL CHANGES IN A RABBIT MODEL OF VOCAL FOLD DEHYDRATION

There is a considerable body of evidence suggestive that dehydration can negatively impact voice production. However, our understanding of the underlying biology and physiological changes, particularly at the molecular level,  that contribute to this dysphonia are limited. Further, our ability to assess underlying changes in humans is restricted largely to post-mortem tissue or tissue resected during interventional vocal fold surgery, both of which are subject to bias in age and disease state. Here we have utilized a New Zealand white rabbit model of vocal fold dehydration to probe the in vivo molecular response to dehydration, focusing on differential gene and protein regulation. In the first study, a single 8-hour exposure to low humidity was used to induce airway surface dehydration. RNA Sequencing was used to obtain a global snapshot of differential transcriptional regulation. This informed a second study wherein 8-hour exposures to low humidity over 15 consecutive days were used and followed by LC-MS/MS proteomic analysis to interrogate potential functional changes. In the third study, systemic dehydration was induced with a 5-day water restriction protocol. A third rehydrated group was included that returned to ad libitum consumption for 3 days. LC-MS/MS proteomic analysis was used. We have found evidence for transcriptional and protein expression changes under both dehydration paradigms. Our findings serve to inform our molecular biological understanding of dehydration of the vocal folds with implications to prophylaxis against and clinical intervention thereof.