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Nagoya Journal of Medical Science Feb 2017The inner and middle ear are connected mainly through round and oval windows, and inflammation in the middle ear cavity can spread into the inner ear, which might induce... (Review)
Review
The inner and middle ear are connected mainly through round and oval windows, and inflammation in the middle ear cavity can spread into the inner ear, which might induce a disturbance. In cases with intractable otitis media, attention should also be paid to symptoms related to the inner ear. In this paper, middle ear inflammation and related inner ear disturbances are reviewed with a focus on representative middle ear diseases (such as acute otitis media, chronic otitis media, otitis media with anti-neutrophil cytoplasmic antibody-associated vasculitis, eosinophilic otitis media, cholesteatoma with labyrinthine fistula, and reflux-related otitis media). Their clinical concerns are then discussed with reference to experimental studies. In these diseases, early diagnosis and adequate treatment are required to manage not only middle ear but also inner ear conditions.
Topics: Ear, Inner; Ear, Middle; Humans; Inflammation; Otitis Media
PubMed: 28303055
DOI: 10.18999/nagjms.79.1.1 -
Development (Cambridge, England) Jun 2023The inner ear sensory epithelia contain mechanosensitive hair cells and supporting cells. Both cell types arise from SOX2-expressing prosensory cells, but the mechanisms...
The inner ear sensory epithelia contain mechanosensitive hair cells and supporting cells. Both cell types arise from SOX2-expressing prosensory cells, but the mechanisms underlying the diversification of these cell lineages remain unclear. To determine the transcriptional trajectory of prosensory cells, we established a SOX2-2A-ntdTomato human embryonic stem cell line using CRISPR/Cas9, and performed single-cell RNA-sequencing analyses with SOX2-positive cells isolated from inner ear organoids at various time points between differentiation days 20 and 60. Our pseudotime analysis suggests that vestibular type II hair cells arise primarily from supporting cells, rather than bi-fated prosensory cells in organoids. Moreover, ion channel- and ion-transporter-related gene sets were enriched in supporting cells versus prosensory cells, whereas Wnt signaling-related gene sets were enriched in hair cells versus supporting cells. These findings provide valuable insights into how prosensory cells give rise to hair cells and supporting cells during human inner ear development, and may provide a clue to promote hair cell regeneration from resident supporting cells in individuals with hearing loss or balance disorders.
Topics: Humans; Organoids; Hair Cells, Auditory; Hair Cells, Vestibular; Vestibule, Labyrinth; Cell Differentiation
PubMed: 37381908
DOI: 10.1242/dev.201071 -
Genes Nov 2020The etiology of hearing impairment following cochlear damage can be caused by many factors, including congenital or acquired onset, ototoxic drugs, noise exposure, and... (Review)
Review
The etiology of hearing impairment following cochlear damage can be caused by many factors, including congenital or acquired onset, ototoxic drugs, noise exposure, and aging. Regardless of the many different etiologies, a common pathologic change is auditory cell death. It may be difficult to explain hearing impairment only from the aspect of cell death including apoptosis, necrosis, or necroptosis because the level of hearing loss varies widely. Therefore, we focused on autophagy as an intracellular phenomenon functionally competing with cell death. Autophagy is a dynamic lysosomal degradation and recycling system in the eukaryotic cell, mandatory for controlling the balance between cell survival and cell death induced by cellular stress, and maintaining homeostasis of postmitotic cells, including hair cells (HCs) and spiral ganglion neurons (SGNs) in the inner ear. Autophagy is considered a candidate for the auditory cell fate decision factor, whereas autophagy deficiency could be one of major causes of hearing impairment. In this paper, we review the molecular mechanisms and biologic functions of autophagy in the auditory system and discuss the latest research concerning autophagy-related genes and sensorineural hearing loss to gain insight into the role of autophagic mechanisms in inner-ear disorders.
Topics: Apoptosis; Autophagy; Cell Death; Ear, Inner; Hair Cells, Auditory; Hearing; Hearing Loss; Humans; Neurons; Spiral Ganglion
PubMed: 33187328
DOI: 10.3390/genes11111331 -
Autoimmunity Reviews Aug 2012To review our current knowledge of the pathogenesis of Meniere's disease, including viral infection and immune system-mediated mechanisms, and to discuss the... (Review)
Review
OBJECTIVES
To review our current knowledge of the pathogenesis of Meniere's disease, including viral infection and immune system-mediated mechanisms, and to discuss the pathogenesis as it relates to pharmacotherapy.
SYSTEMATIC REVIEW METHODOLOGY
Relevant publications on the aetiopathogenesis, molecular biology, genetics and histopathology of Meniere's disease from 1861 to 2011 were analysed.
RESULTS AND CONCLUSIONS
Meniere's disease is characterised by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure. The aetiology and pathogenesis remain unknown. Proposed theories of causation include viral infections and immune system-mediated mechanisms. The immune response in Meniere's disease is focused on inner ear antigens. Approximately one-third of Meniere's disease cases seem to be of an autoimmune origin although the immunological mechanisms involved are not clear. The diagnosis of autoimmune inner ear disease is based either on clinical criteria or on a positive response to steroids. The antiviral approach has virtually eliminated the use of various surgical methods used in the past. Steroid responsiveness is high, and with prompt treatment, inner ear damage may be reversible. The administration of etanercept improves or stabilises symptoms in treated patients. Treatment of antiphospholipid syndrome can be directed toward preventing thromboembolic events by using antithrombotic medications. Only warfarin has been shown to be effective. Gene therapy can be used to transfer genetic material into inner ear cells using viral vectors and to protect, rescue, and even regenerate hair cells of the inner ear.
Topics: Animals; Autoimmune Diseases; Ear, Inner; Humans; Meniere Disease
PubMed: 22306860
DOI: 10.1016/j.autrev.2012.01.004 -
Stem Cell Reports Jun 2020Sensorineural hearing loss and vestibular dysfunction are caused by damage to neurons and mechanosensitive hair cells, which do not regenerate to any clinically relevant... (Review)
Review
Sensorineural hearing loss and vestibular dysfunction are caused by damage to neurons and mechanosensitive hair cells, which do not regenerate to any clinically relevant extent in humans. Several protocols have been devised to direct pluripotent stem cells (PSCs) into inner ear hair cells and neurons, which display many properties of their native counterparts. The efficiency, reproducibility, and scalability of these protocols are enhanced by incorporating knowledge of inner ear development. Modeling human diseases in vitro through genetic manipulation of PSCs is already feasible, thereby permitting the elucidation of mechanistic understandings of a wide array of disease etiologies. Early studies on transplantation of PSC-derived otic progenitors have been successful in certain animal models, yet restoration of function and long-term cell survival remain unrealized. Through further research, PSC-based approaches will continue to revolutionize our understanding of inner ear biology and contribute to the development of therapeutic treatments for inner ear disorders.
Topics: Animals; Ear, Inner; Hearing Loss, Sensorineural; Humans; Neural Stem Cells; Neurogenesis; Pluripotent Stem Cells; Stem Cell Transplantation
PubMed: 32442531
DOI: 10.1016/j.stemcr.2020.04.008 -
Integrative and Comparative Biology Aug 2018During rapid locomotion, the vestibular inner ear provides head-motion signals that stabilize posture, gaze, and heading. Afferent nerve fibers from central and... (Review)
Review
During rapid locomotion, the vestibular inner ear provides head-motion signals that stabilize posture, gaze, and heading. Afferent nerve fibers from central and peripheral zones of vestibular sensory epithelia use temporal and rate encoding, respectively, to emphasize different aspects of head motion: central afferents adapt faster to sustained head position and favor higher stimulus frequencies, reflecting specializations at each stage from motion of the accessory structure to spike propagation to the brain. One specialization in amniotes is an unusual nonquantal synaptic mechanism by which type I hair cells transmit to large calyceal terminals of afferent neurons. The reduced synaptic delay of this mechanism may have evolved to serve reliable and fast input to reflex pathways that ensure stable locomotion on land.
Topics: Animals; Ear, Inner; Hair Cells, Vestibular; Neurons, Afferent; Signal Transduction; Vertebrates
PubMed: 29920589
DOI: 10.1093/icb/icy069 -
AJNR. American Journal of Neuroradiology Jan 2017Third window abnormalities are defects in the integrity of the bony structure of the inner ear, classically producing sound-/pressure-induced vertigo (Tullio and... (Review)
Review
Third window abnormalities are defects in the integrity of the bony structure of the inner ear, classically producing sound-/pressure-induced vertigo (Tullio and Hennebert signs) and/or a low-frequency air-bone gap by audiometry. Specific anatomic defects include semicircular canal dehiscence, perilabyrinthine fistula, enlarged vestibular aqueduct, dehiscence of the scala vestibuli side of the cochlea, X-linked stapes gusher, and bone dyscrasias. We discuss these various entities and provide key examples from our institutional teaching file with a discussion of symptomatology, temporal bone CT, audiometry, and vestibular-evoked myogenic potentials.
Topics: Ear, Inner; Humans; Labyrinth Diseases
PubMed: 27561833
DOI: 10.3174/ajnr.A4922 -
Scientific Reports Feb 2021Brain atlases and templates are core tools in scientific research with increasing importance also in clinical applications. Advances in neuroimaging now allowed us to... (Clinical Trial)
Clinical Trial
Brain atlases and templates are core tools in scientific research with increasing importance also in clinical applications. Advances in neuroimaging now allowed us to expand the atlas domain to the vestibular and auditory organ, the inner ear. In this study, we present IE-Map, an in-vivo template and atlas of the human labyrinth derived from multi-modal high-resolution magnetic resonance imaging (MRI) data, in a fully non-invasive manner without any contrast agent or radiation. We reconstructed a common template from 126 inner ears (63 normal subjects) and annotated it with 94 established landmarks and semi-automatic segmentations of all relevant macroscopic vestibular and auditory substructures. We validated the atlas by comparing MRI templates to a novel CT/micro-CT atlas, which we reconstructed from 21 publicly available post-mortem images of the bony labyrinth. Templates in MRI and micro-CT have a high overlap, and several key anatomical measures of the bony labyrinth in IE-Map are in line with micro-CT literature of the inner ear. A quantitative substructural analysis based on the new template, revealed a correlation of labyrinth parameters with total intracranial volume. No effects of gender or laterality were found. We provide the validated templates, atlas segmentations, surface meshes and landmark annotations as open-access material, to provide neuroscience researchers and clinicians in neurology, neurosurgery, and otorhinolaryngology with a widely applicable tool for computational neuro-otology.
Topics: Adult; Female; Humans; Magnetic Resonance Imaging; Male; Vestibule, Labyrinth; X-Ray Microtomography
PubMed: 33558581
DOI: 10.1038/s41598-021-82716-0 -
Journal of Anatomy Feb 2016The identification of transcriptional differences has served as an important starting point in understanding the molecular mechanisms behind biological processes and... (Review)
Review
The identification of transcriptional differences has served as an important starting point in understanding the molecular mechanisms behind biological processes and systems. The developmental biology of the inner ear, the biology of hearing and of course the pathology of deafness are all processes that warrant a molecular description if we are to improve human health. To this end, technological innovation has meant that larger scale analysis of gene transcription has been possible for a number of years now, extending our molecular analysis of genes to beyond those that are currently in vogue for a given system. In this review, some of the contributions gene profiling has made to understanding developmental, pathological and physiological processes in the inner ear are highlighted.
Topics: Animals; Deafness; Ear, Inner; Gene Expression Profiling; Hearing; Humans; Microarray Analysis
PubMed: 26403558
DOI: 10.1111/joa.12376 -
Cell Death and Differentiation Jan 2021While inner ear disorders are common, our ability to intervene and recover their sensory function is limited. In vitro models of the inner ear, like the organoid system,... (Review)
Review
While inner ear disorders are common, our ability to intervene and recover their sensory function is limited. In vitro models of the inner ear, like the organoid system, could aid in identifying new regenerative drugs and gene therapies. Here, we provide a perspective on the status of in vitro inner ear models and guidance on how to improve their applicability in translational research. We highlight the generation of inner ear cell types from pluripotent stem cells as a particularly promising focus of research. Several exciting recent studies have shown how the developmental signaling cues of embryonic and fetal development can be mimicked to differentiate stem cells into "inner ear organoids" containing otic progenitor cells, hair cells, and neurons. However, current differentiation protocols and our knowledge of embryonic and fetal inner ear development in general, have a bias toward the sensory epithelia of the inner ear. We propose that a more holistic view is needed to better model the inner ear in vitro. Moving forward, attention should be made to the broader diversity of neuroglial and mesenchymal cell types of the inner ear, and how they interact in space or time during development. With improved control of epithelial, neuroglial, and mesenchymal cell fate specification, inner ear organoids would have the ability to truly recapitulate neurosensory function and dysfunction. We conclude by discussing how single-cell atlases of the developing inner ear and technical innovations will be critical tools to advance inner ear organoid platforms for future pre-clinical applications.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Cells, Cultured; Ear, Inner; Epithelium; Hair Cells, Auditory, Inner; Humans; Models, Biological; Organoids; Pluripotent Stem Cells
PubMed: 33318601
DOI: 10.1038/s41418-020-00678-8