Emerging Mechanisms in the Pathogenesis of Menière’s Disease: Evidence for the Involvement of Ion Homeostatic or Blood–Labyrinthine Barrier Dysfunction in Human Temporal Bones

Author:

Johns J. Dixon,Olszewski Rafal1,Strepay Dillon1,Lopez Ivan A.2,Ishiyama Akira2,Hoa Michael

Affiliation:

1. Auditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland

2. Department of Head and Neck Surgery, University of California School of Medicine, Los Angeles, California

Abstract

Hypothesis Analysis of human temporal bone specimens of patients with Menière’s disease (MD) may demonstrate altered expression of gene products related to barrier formation and ionic homeostasis within cochlear structures compared with control specimens Background MD represents a challenging otologic disorder for investigation. Despite attempts to define the pathogenesis of MD, there remain many gaps in our understanding, including differences in protein expression within the inner ear. Understanding these changes may facilitate the identification of more targeted therapies for MD. Methods Human temporal bones from patients with MD (n = 8) and age-matched control patients (n = 8) were processed with immunohistochemistry stains to detect known protein expression related to ionic homeostasis and barrier function in the cochlea, including CLDN11, CLU, KCNJ10, and SLC12A2. Immunofluorescence intensity analysis was performed to quantify protein expression in the stria vascularis, organ of Corti, and spiral ganglion neuron (SGN). Results Expression of KCNJ10 was significantly reduced in all cochlear regions, including the stria vascularis (9.23 vs 17.52, p = 0.011), OC (14.93 vs 29.16, p = 0.014), and SGN (7.69 vs 18.85, p = 0.0048) in human temporal bone specimens from patients with MD compared with control, respectively. CLDN11 (7.40 vs 10.88, p = 0.049) and CLU (7.80 vs 17.51, p = 0.0051) expression was significantly reduced in the SGN. Conclusion The results of this study support that there may be differences in the expression of proteins related to ionic homeostasis and barrier function within the cochlea, potentially supporting the role of targeted therapies to treat MD.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Neurology (clinical),Sensory Systems,Otorhinolaryngology

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