Morphological changes of the endolymphatic sac induced by microinjection of artificial endolymph into the cochlea

Rask‐Andersen, Helge; DeMott, John E.; Bagger‐Sjöbäck, Dan; Salt, Alec N.

doi:10.1016/s0378-5955(99)00153-7

Cited by 48 publications

(49 citation statements)

References 10 publications

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“…Then, after being released, it is transported to the ES by means of longitudinal flow, and is eliminated by macropinocytosis. However, pre- vious studies have suggested that the ES epithelial cells may be capable of secreting proteinaceous substances (Kimura and Schuknecht, 1965;Lundquist, 1965;Friberg et al, 1986;Erwall et al, 1988;Rask-Andersen et al, 1999). Hence, we cannot rule out the possibility that the soluble megalin is generated by alternative RNA splicing and is exocytosed into the lumen of the ES.…”

Section: Discussionmentioning

confidence: 89%

“…These macromolecules are taken up and degraded by free-floating cells such as luminal macrophages and lymphoid cells. The ES is believed to play an important role in maintaining homeostasis in the inner ear, by the absorption and secretion of endolymph (Kimura and Schuknecht, 1965;Lundquist, 1965;Friberg et al, 1986;Erwall et al, 1988;Rask-Andersen et al, 1999), pressure regulation in the endolymphatic compartment (Rask-Andersen et al, 1987), immunodefense of the inner ear (Rask-Andersen and Stahle, 1980;Tomiyama and Harris, 1986), the removal of waste products and foreign materials from the endolymphatic space (Fukazawa et al, 1991), and endocrine function (Qvortrup and Bretlau, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Soluble Megalin Is Accumulated in the Lumen of the Rat Endolymphatic Sac

Ishida

Hatae

Nishi

et al. 2006

Cell Struct. Funct.

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ABSTRACT. The endolymphatic sac (ES) is believed to play an important role in maintaining homeostasis in the inner ear by the absorption and endocytosis of endolymph. Megalin is a 600-kDa multiligand endocytic receptor expressed in certain types of absorptive epithelia including kidney proximal tubules. We analyzed the immunoreactivity for megalin in rat ES by immunofluorescence, immunogold electron microscopy, and immunoblotting. With immunostaining, the luminal substances of the ES were strongly stained for megalin. Megalin was also localized in luminal macrophage-like cells and both types of epithelial cell (mitochondria-rich cells and ribosomerich cells). In these cells, the megalin was localized in the lumen of endosomes, but was not membrane associated. This localization pattern indicates that the megalin in these cells is not a membrane receptor, but merely one of the constituents that are endocytosed from the lumen of the ES. Immunoblotting indicated that the megalin in the ES is a 210-kDa molecule lacking a cytoplasmic domain. This suggests that the megalin in the ES may be a soluble form, different from the 600-kDa membrane-bound receptor expressed in kidneys. Taken together, it is likely that the megalin in the ES lumen is a soluble component and may be endocytosed by the ES epithelial cells. Furthermore, we found that the tectorial membrane, an acellular structure in the cochlea, gave a strong megalin immunoreaction. Since the cochlea is connected to the ES, the megalin may be transported alone or with the components of the tectorial membrane from the cochlea to the ES lumen through longitudinal flow.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Soluble Megalin Is Accumulated in the Lumen of the Rat Endolymphatic Sac

Ishida

Hatae

Nishi

et al. 2006

Cell Struct. Funct.

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“…Volume expansion led to a marked decrease of the density of the "homogeneous substance", believed to consist of glycoproteins, whereas endolymph contraction had the opposite effect. As a result the authors [6] proposed that the macromolecules in question may play an essential role in endolymph volume regulation, and may be instrumental in the pathogenesis of Meniere's disease.…”

Section: Endolymphatic Sac -Physiological Significance and Role In Mementioning

confidence: 99%

“…A promising strategy for the detection and/or identification of the macromolecule(s) corresponding to the "homogeneous substance" would be to search for substances that exhibit a significant increase and/or decrease in density in response to experimental contraction and/ or expansion of endolymph volume [6,24]. To facilitate evaluation, we are in the process of implementing 2-D differential gel electrophoretic analysis based on Cy3 and Cy5 dye labeling for the two conditions.…”

Section: Esmentioning

confidence: 99%

Microscale analysis of proteins in inner ear tissues and fluids with emphasis on endolymphatic sac, otoconia, and organ of Corti

Thalmann

Hughes²,

Tong

et al. 2006

Electrophoresis

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Here we describe preparatory techniques adapted for the study of proteins of inner ear tissues and fluids that have allowed us to apply state-of-the-art analytical techniques in spite of the minute size and anatomical complexities of this organ. Illustrative examples address unresolved issues of functional and clinical significance. First, we demonstrate how quick-freezing and freeze drying prevents artifacts that arise from sampling endolymphatic sac (ES) content in the liquid state. This set the stage for the generation of the first protein profile of the ES. Identification of crucial proteins will help elucidate mechanisms of endolymph volume regulation and pathogenesis of Meniere's disease. Second, we show how a unique situation allowed identification of otoconial proteins by mass spectrometric analysis without prior separation and we discuss possible roles for these minor otoconins in otoconial development and prevention of degenerative diseases that affect balance. Finally, we demonstrate techniques for the precise dissection of organ of Corti and its substructures, while preserving their near normal chemical state. We extended an earlier study in which we identified a novel calcium-binding protein by IEF, oncomodulin, localized in the outer hair cells and show here the applicability of prefractionation for the screening of calcium-binding proteins of organ of Corti. These studies demonstrate how advanced preparatory and analytical techniques can be applied to studies of the inner ear.

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“…From these data it is not possible to verify whether the ES response may have a protective role for the inner ear function, since the number of animals with hearing loss did not differ significantly between groups of animals with reactive versus nonreactive sacs. The reason for this might be the rapid fluid transport and turnover in the ES which might escape the investigator from seeing changes [13], as the animals of this study were sacrificed as long as 1 week after toxin exposure.…”

Section: Discussionmentioning

confidence: 99%

Middle Ear Exotoxin and Endolymphatic Sac Response: An Immune Reaction?

Nordang¹,

Anniko²,

Rask‐Andersen³

2000

Otorhinolaryngol Nova

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Objectives: The endolymphatic sac (ES) is presumed to be involved in immune response in the inner ear. The ES has been shown to respond immunologically to an antigen instilled into the scala tympani. Pseudomonas aeruginosa exotoxin A (PaExoA) is known to pass the round window membrane and to cause cochlear functional impairment. Does the ES in the inner ear respond immunologically to exotoxin exposed in the middle ear? Methods: In the present study, the ES was examined morphologically after application of PaExoA in the middle ear of the rat. The ES changes were correlated with electrophysiological results using ABR measurements. Results: In 18 out of 32 exposed ES we found signs of inflammatory activity with raised numbers of intraluminal macrophages together with signs of epithelial alterations. There were also changes in character and stainability of the intraluminal glycoprotein conjugates. Conclusions: The ES changes may either be due to a direct exposure of toxin to the ES or possibly represent the expression of an augmented general response in the inner ear. These findings are similar to earlier descriptions of changes in the ES after experimental labyrinthitis. This is the first presentation showing altered ES activity following middle ear application of exotoxin.

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Morphological changes of the endolymphatic sac induced by microinjection of artificial endolymph into the cochlea

Cited by 48 publications

References 10 publications

Soluble Megalin Is Accumulated in the Lumen of the Rat Endolymphatic Sac

Soluble Megalin Is Accumulated in the Lumen of the Rat Endolymphatic Sac

Microscale analysis of proteins in inner ear tissues and fluids with emphasis on endolymphatic sac, otoconia, and organ of Corti

Middle Ear Exotoxin and Endolymphatic Sac Response: An Immune Reaction?

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