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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 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Apr 2021As isolated anatomical position, limited labyrinthine artery supply, and blood-labyrinth barrier hampers systemic drug delivery to the inner ear. The efficient... (Review)
Review
As isolated anatomical position, limited labyrinthine artery supply, and blood-labyrinth barrier hampers systemic drug delivery to the inner ear. The efficient concentration of drug treatment is unsatisfactory and there's possible side effects after systemic administration. Intratympanic injection of drug can bypass the blood-labyrinth and permeated to the hair cells or synaptic area via the round-or oval window of the cochlea. Efficacy and safety of pharmacotherapy has become increasingly relied on the inner ear delivery carrier system. The goal of this review focus on the anatomical barrier that need to be overcome in the intratympanic applications, the improvement of drug retention and specific targets, and the safety of novel drug carriers, these emerging strategies of local drug delivery promise novel and better guidance for the clinical application.
Topics: Cochlea; Drug Carriers; Drug Delivery Systems; Ear, Inner; Round Window, Ear
PubMed: 33794643
DOI: 10.13201/j.issn.2096-7993.2021.04.022 -
Neuroscience Letters Sep 2019Acquisition of cell polarity generates signaling and cytoskeletal asymmetry and thus underpins polarized cell behaviors during tissue morphogenesis. In epithelial... (Review)
Review
Acquisition of cell polarity generates signaling and cytoskeletal asymmetry and thus underpins polarized cell behaviors during tissue morphogenesis. In epithelial tissues, both apical-basal polarity and planar polarity, which refers to cell polarization along an axis orthogonal to the apical-basal axis, are essential for epithelial morphogenesis and function. A prime example of epithelial planar polarity can be found in the auditory sensory epithelium (or organ of Corti, OC). Sensory hair cells, the sound receptors, acquire a planar polarized apical cytoskeleton which is uniformely oriented along an axis orthogonal to the longitudinal axis of the cochlear duct. Both cell-intrinsic and tissue-level planar polarity are necessary for proper perception of sound. Here we review recent insights into the novel roles and mechanisms of planar polarity signaling gained from genetic analysis in mice, focusing mainly on the OC but also with some discussions on the vestibular sensory epithelia.
Topics: Animals; Cell Polarity; Ear, Inner; Hair Cells, Auditory; Hair Cells, Auditory, Inner; Humans; Organ of Corti; Stereocilia
PubMed: 31295539
DOI: 10.1016/j.neulet.2019.134373 -
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 -
Hearing Research Nov 2015Bone conduction (BC) hearing relies on sound vibration transmission in the skull bone. Several clinical findings indicate that in the human, the skull vibration of the... (Review)
Review
Bone conduction (BC) hearing relies on sound vibration transmission in the skull bone. Several clinical findings indicate that in the human, the skull vibration of the inner ear dominates the response for BC sound. Two phenomena transform the vibrations of the skull surrounding the inner ear to an excitation of the basilar membrane, (1) inertia of the inner ear fluid and (2) compression and expansion of the inner ear space. The relative importance of these two contributors were investigated using an impedance lumped element model. By dividing the motion of the inner ear boundary in common and differential motion it was found that the common motion dominated at frequencies below 7 kHz but above this frequency differential motion was greatest. When these motions were used to excite the model it was found that for the normal ear, the fluid inertia response was up to 20 dB greater than the compression response. This changed in the pathological ear where, for example, otosclerosis of the stapes depressed the fluid inertia response and improved the compression response so that inner ear compression dominated BC hearing at frequencies above 400 Hz. The model was also able to predict experimental and clinical findings of BC sensitivity in the literature, for example the so called Carhart notch in otosclerosis, increased BC sensitivity in superior semicircular canal dehiscence, and altered BC sensitivity following a vestibular fenestration and RW atresia.
Topics: Biomechanical Phenomena; Bone Conduction; Cochlea; Ear, Inner; Electric Impedance; Humans; Labyrinthine Fluids; Models, Biological; Oval Window, Ear; Round Window, Ear; Vibration
PubMed: 25528492
DOI: 10.1016/j.heares.2014.12.003 -
Hearing Research Oct 2018
Topics: Animals; Drug Delivery Systems; Ear, Inner; Hearing; Hearing Loss; Humans; Labyrinth Diseases; Pharmaceutical Preparations
PubMed: 30006112
DOI: 10.1016/j.heares.2018.06.018 -
Anatomical Record (Hoboken, N.J. : 2007) Nov 2012This is a review of the biological processes and the main signaling pathways required to generate the different otic cell types, with particular emphasis on the actions... (Review)
Review
This is a review of the biological processes and the main signaling pathways required to generate the different otic cell types, with particular emphasis on the actions of insulin-like growth factor I. The sensory organs responsible of hearing and balance have a common embryonic origin in the otic placode. Lineages of neural, sensory, and support cells are generated from common otic neuroepithelial progenitors. The sequential generation of the cell types that will form the adult inner ear requires the coordination of cell proliferation with cell differentiation programs, the strict regulation of cell survival, and the metabolic homeostasis of otic precursors. A network of intracellular signals operates to coordinate the transcriptional response to the extracellular input. Understanding the molecular clues that direct otic development is fundamental for the design of novel treatments for the protection and repair of hearing loss and balance disorders.
Topics: Animals; Cell Differentiation; Ear, Inner; Gene Expression Regulation, Developmental; Humans; Signal Transduction; Vertebrates
PubMed: 23044927
DOI: 10.1002/ar.22575