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.
Highlights
Meniere’s disease (MD) [36] is a syndrome that affects the inner ear
The latter is suggested by various observations: (1) many precipitating and exacerbating factors have been associated with MD [39, 45]; (2) the frequency, duration and severity of symptoms are highly variable within and between MD patients [17], (3) other disorders can present with similar symptoms [19, 21], (4) the overaccumulation of endolymphatic fluid in the inner ear, i.e., endolymphatic hydrops (EH), long considered the underlying pathology and cause of MD [52, 22, 20, 41, 32], has been observed in patients without MD symptoms [46, 33] and in cases of other otological diseases (secondary EH; [46, 33] or no otological disease (asymptomatic EH; [37, 43]; and (5) despite many histopathological studies, no distinctive cellular or molecular pathology has been consistently linked to MD
We demonstrated here that degenerative pathology (Fig. 8c, lower left panel) and developmental hypoplasia of the extraosseous portion of the endolymphatic sac (eES) (Fig. 8c, lower right panel) are consistently and associated with idiopathic EH, since both pathologies were found in 13/14 patients (95.8%) with idiopathic EH but only 1/39 patients (2.6%) with secondary EH and no controls
Summary
Meniere’s disease (MD) [36] is a syndrome that affects the inner ear. MD is defined and diagnosed based on recurrent fluctuant vestibular (rotational vertigo) and auditory (hearing loss, tinnitus, aural fullness) symptoms [4, 31]. MD is generally acknowledged as a definable clinical entity, it remains unclear whether only one etiopathology exists or whether multiple different pathologies can elicit the characteristic symptoms The latter is suggested by various observations: (1) many precipitating and exacerbating factors have been associated with MD [39, 45]; (2) the frequency, duration and severity of symptoms are highly variable within and between MD patients [17], (3) other disorders can present with similar symptoms [19, 21], (4) the overaccumulation of endolymphatic fluid in the inner ear, i.e., (idiopathic) endolymphatic hydrops (EH), long considered the underlying pathology and cause of MD [52, 22, 20, 41, 32], has been observed in patients without MD symptoms [46, 33] and in cases of other otological diseases (secondary EH; [46, 33] or no otological disease (asymptomatic EH; [37, 43]; and (5) despite many histopathological studies (reviewed in [48, 34]), no distinctive cellular or molecular pathology has been consistently linked to MD. The channel/transport proteins and ALDOrelated signaling molecules we found in the ES are similar to those in the ALDO-sensitive distal nephron, where highly regulated, ALDO-dependent Na+ reabsorption is carried out to maintain whole-body sodium and volume homeostasis (reviewed in [30])
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