Increased Adrenergic Receptor Expression in Meniere Disease.

HYPOTHESIS: There is increased expression of adrenergic receptors in the vestibular end organs of Meniere disease.

BACKGROUND

Meniere disease (MD) is an inner ear condition characterized by episodic vertigo, hearing loss, tinnitus, and aural fullness. It is believed to be due to an imbalance in inner ear fluid, often leading to hydrops; however, the exact mechanism is unclear. Pupillometry data have suggested a role for autonomic dysfunction, specifically sympathetic hyperactivity, but few studies have investigated the molecular pathways involved in this.

METHODS

Vestibular end organs from patients undergoing labyrinthectomy for MD (n=6), as well as control specimens (n=3) from patients with vestibular schwannoma undergoing translabyrinthine resection, were collected and processed for RNA in situ hybridization using the RNAscope Multiplex Fluorescent V2 Assay with probes for β 1 -, β 2 -, and α 1a -adrenergic receptors (AR). Positive and negative control experiments were also performed for quality control. Immunofluorescence was used to characterize protein expression of α 1a -AR and to identify vestibular hair cells (VHC) in the sensory epithelium (Myosin VIIa).

RESULTS

There is increased expression of α 1a -AR transcripts in MD utricles compared with control. This appears to be concentrated in the sensory epithelium VHC, confirmed with MyoVIIa positivity, although expression can be seen in the stroma as well. This was further confirmed with immunofluorescence, demonstrating increased expression in MD. There is also transcriptional expression of β 2 -AR with no difference between the 2 groups.

CONCLUSIONS

There are limited molecular studies investigating the pathogenesis of MD, especially those utilizing human surgical tissue. This is the first study to demonstrate increased expression of α 1a -AR both at the transcriptional and protein levels in MD compared with controls. These results may help explain the mechanism behind sympathetic hyperactivity and guide future therapies.