Abstract
Hearing and balance functions of the inner ear rely on the homeostasis of the endolymphatic fluid. When disturbed, pathologic endolymphatic hydrops evolves as observed in Menière’s disease. The molecular basis of inner ear fluid regulation across the endolymphatic epithelium is largely unknown. In this study we identified the specific expression of the tight junction (TJ) molecules Claudin 3, 4, 6, 7, 8, 10, and 16 in epithelial preparations of the rat inner ear endolymphatic duct (ED) and endolymphatic sac (ES) by high-throughput qPCR and immunofluorescence confocal microscopy. Further we showed that Claudin 4 in the ES is a target of arginine-vasopressin (AVP), a hormone elevated in Menière’s disease. Moreover, our transmission-electron microscopy (TEM) analysis revealed that the TJs of the ED were shallow and shorter compared to the TJ of the ES indicating facilitation of a paracellular fluid transport across the ED epithelium. The significant differences in the subcellular localization of the barrier-forming protein Claudin 3 between the ED and ES epithelium further support the TEM observations. Our results indicate a high relevance of Claudin 3 and Claudin 4 as important paracellular barrier molecules in the ED and ES epithelium with potential involvement in the pathophysiology of Menière’s disease.
Highlights
Visualized the inner ear fluid movements by light sheet fluorescence microscopy after the injection of fluorescein isothiocyanateedextran into scala media and found a remarkable uptake of the fluorescence marker into the endolymphatic duct and the periductal channels[27]
The ribosome rich like cells showed basal invaginations and the endolymphatic duct (ED) epithelium was surrounded by a dense subepithelial capillary network (Fig. 2a) with endothelial cells connected by prominent TJ with numerous kissing points
The transmission electron microscopy (TEM) analysis revealed that the tight junctions of the ED epithelium were generally shorter and with considerably less membranous kissing points compared to the endolymphatic sac (ES) epithelium
Summary
Visualized the inner ear fluid movements by light sheet fluorescence microscopy after the injection of fluorescein isothiocyanateedextran into scala media and found a remarkable uptake of the fluorescence marker into the endolymphatic duct and the periductal channels[27]. Almost no progress has been made in further elucidating the mechanisms of the paracellular fluid and ion homeostasis in the different parts of the ED or ES. The first aim of this study was to analyze the expression of different members of the claudin family in the ED and to compare it with that of the ES to gain insights into the role of TJs in these epithelia. Several clinical and experimental studies suggest arginine vasopressin (AVP) as a potential regulator of endolymphatic fluid and ion homeostasis[30,31,32].
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