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Inner ear pathologies impair sodium-regulated ion transport in Meniere's disease
Andreas H Eckhard1,2, MengYu Zhu3, Jennifer T O'Malley3
1Otopathology Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA, USA. AndreasHeinrich.Eckhard@usz.ch.
Abstract:
Meniere's disease (MD), a syndromal inner ear disease, is commonly associated with a pathological accumulation of endolymphatic fluid in the inner ear, termed "idiopathic" endolymphatic hydrops (iEH). Although numerous precipitating/exacerbating factors have been proposed for MD, its etiology remains elusive. Here, using immunohistochemistry and in situ protein-protein interaction detection assays, we demonstrate mineralocorticoid-controlled sodium transport mechanisms in the epithelium of the extraosseous portion of the endolymphatic sac (eES) in the murine and human inner ears. Histological analysis of the eES in an extensive series of human temporal bones consistently revealed pathological changes in the eES in cases with iEH and a clinical history of MD, but no such changes were found in cases with "secondary" EH due to other otological diseases or in healthy controls. Notably, two etiologically different pathologies-degeneration and developmental hypoplasia-that selectively affect the eES in MD were distinguished. Clinical records from MD cases with degenerative and hypoplastic eES pathology revealed distinct intergroup differences in clinical disease presentation. Overall, we have identified for the first time two inner ear pathologies that are consistently present in MD and can be directly linked to the pathogenesis of EH, and which potentially affect the phenotypical presentation of MD.
Insights
Researchers identified two distinct inner ear pathologies in Meniere's disease (MD) patients, linked to fluid buildup (endolymphatic hydrops) and potentially influencing disease presentation.
Area of Science:
- Otolaryngology
- Inner Ear Pathophysiology
- Molecular Biology
Background:
- Meniere's disease (MD) is characterized by endolymphatic hydrops (EH), but its exact cause remains unknown.
- Proposed factors for MD exacerbation lack definitive etiological links.
- Understanding the pathogenesis of EH is crucial for MD treatment.
Purpose of the Study:
- To investigate the role of mineralocorticoid-controlled sodium transport in the endolymphatic sac (ES) in MD.
- To identify specific pathological changes in the extraosseous portion of the ES (eES) associated with MD and EH.
- To correlate eES pathologies with clinical disease presentation in MD patients.
Main Methods:
- Immunohistochemistry and in situ protein-protein interaction assays in murine and human inner ear samples.
- Histological analysis of the eES in human temporal bones from MD patients and controls.
- Correlation of eES pathology with clinical records of MD patients.
Main Results:
- Demonstrated mineralocorticoid-regulated sodium transport mechanisms in the eES epithelium.
- Identified consistent pathological changes (degeneration and hypoplasia) in the eES of MD patients with idiopathic EH (iEH).
- Found no similar eES pathology in secondary EH or healthy controls.
- Observed distinct clinical presentations correlating with degenerative versus hypoplastic eES pathologies.
Conclusions:
- Identified two novel inner ear pathologies specifically affecting the eES in Meniere's disease.
- These eES pathologies are directly linked to the pathogenesis of endolymphatic hydrops.
- The identified pathologies may explain the varied clinical phenotypes observed in MD patients.