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Ototoxicity
Published in John C Watkinson, Raymond W Clarke, Christopher P Aldren, Doris-Eva Bamiou, Raymond W Clarke, Richard M Irving, Haytham Kubba, Shakeel R Saeed, Paediatrics, The Ear, Skull Base, 2018
Since organic solvents are minimally water-soluble their distribution in the inner ear is unlikely to be determined by entry into the fluid spaces. It is their distribution in the tissue that is significant. The pattern of damage across the organ of Corti, from outside to in, has suggested that the solvents reach the inner ear from the vasculature of the SV or the spiral prominence region just below it and then pass through the tissues to the organ of Corti.196,201 The cuboidal cells of the outer sulcus and the epithelial cells that connect the epithelia of the lateral wall to the organ of Corti along the basilar membrane may be a major transport route.201 Upon reaching the organ of Corti, the supporting cells of the organ of Corti, the Hensen’s cells that form the outer ridge of the sensory epithelium and the Deiters’ cells that surround the hair cells, may then become injured. Deiters’ cells, in particular those in the outermost row, have been reported to be the most vulnerable cells in the organ of Corti following styrene administration.197,202 The supporting cells are involved in the reuptake of K+ from around the hair cells, and damage to these cells may therefore result in excessive K+ levels around the OHC that would lead to their death. The effects of the solvents may be upon the membranes of the supporting cells and of the hair cells themselves. Loss of membrane integrity and cell swelling, perhaps as a consequence of membrane damage, have been described as early events in the progression of damage in the organ of Corti. Whether the cell death is principally apoptotic202 or necrotic196 is contentious, but it has been reported that the death of Deiters’ cells, unlike that of hair cells, is not prevented by antioxidants, suggesting that different mechanisms of cell death operate in the two cell types.197
Ferroptosis inhibition shields house ear institute-organ of corti 1 cells from free fatty acids-induced inflammatory injuries
Published in Acta Oto-Laryngologica, 2023
Xuemin Chen, Yiding Yu, Ning Yu, Weiwei Guo, Qingqing Jiang, Shiming Yang
It was once thought that Hensen’s cells only played a role in supporting hair cells and stabilizing the three-dimensional structure of the organ of Corti. Some new characteristics of them have been gradually uncovered, including regulating hearing sensitivity and the cochlear partition’s stiffness, maintaining the inner ear lymph ion homeostasis, participating in the mechanical tuning of the cochlea, and facilitating the resolution of inflammatory responses in the inner ear [8]. To the best of our knowledge, Hensen’s cells are the only supporting cells containing lipid droplets (LDs). After noise exposure, LDs are progressively hydrolyzed to produce free fatty acids (FFAs). However, a pivotal unanswered question is the function of LDs in Hensen’s cells and its significance for the organ of Corti as a whole.
Expression of Na/K-ATPase subunits in the human cochlea: a confocal and super-resolution microscopy study with special reference to auditory nerve excitation and cochlear implantation
Published in Upsala Journal of Medical Sciences, 2019
Wei Liu, Maria Luque, Rudolf Glueckert, Niklas Danckwardt-Lillieström, Charlotta Kämpfe Nordström, Anneliese Schrott-Fischer, Helge Rask-Andersen
There have been several studies of Na/K-ATPase expression in the mammalian cochlea over time using various techniques (30,31). A few studies of the human cochlea have been performed (2), and the Na/K-ATPase subtypes in the human auditory periphery are largely unknown. The pattern of heterogeneity of Na/K-ATPase expression in the human auditory nerve may give additional information about its function. Weber et al. (1) performed immunostaining using rabbit polyclonal and mouse monoclonal antibodies to locate isoforms α1, α2, α3, 1, β1, and β2 using the biotin-DAB reaction. The technique detected only the β2 subunit. They found strong staining of nerve endings beneath outer hair cells (OHCs) and IHCs, satellite glial around the spiral ganglion neurons, and the basolateral membrane of stria marginal cells, and moderate reactivity along the lateral cell membrane of the Hensen cells. A strong membrane expression in Hensen cells was found in the present study. It may be relevant considering the rich number of gap junctions expressing connexin30 between these cells that may be responsible for the recirculation of K+ from the organ of Corti to the lateral wall (2,32).
Direct cellular reprogramming and inner ear regeneration
Published in Expert Opinion on Biological Therapy, 2019
Patrick J. Atkinson, Grace S. Kim, Alan G. Cheng
Multiple studies examining Atoh1 and hair cell regeneration have used adenovirus as a means to target supporting cells, such as the pillar cells, Deiters’ cells, as well as Hensen cells [58,59,95]. Specifically, adenovirus serotype 5 has been shown to be efficacious in transducing supporting cells [96]. Adenovirus-mediated Atoh1 studies, however, only found small increases in hair cell number and limited to no recorded functional improvement. In the mature utricle, one study using adenovirus reported hair cell conversion and improved vestibular function by behavioral measures [97]. These studies show that adenovirus can transduce a wide range of supporting cells, highlighting its potential use in future therapies. For a list of information on viral and non-viral approaches, please see Table 1.