Sample records for ear sensory cell

  1. Sensory Cells of the Fish Ear: A Hairy Enigma

    NASA Technical Reports Server (NTRS)

    Popper, A. N.; Saidel, W. M.

    1995-01-01

    Analysis of the structure of the ears in teleost fishes has led to the tentative suggestion that otolithic endorgans may function differently, in different species. Recently, evidence has demonstrated different 'types' of sensory hair cells can be found in the ears of teleost fishes, and individual hair cell types are found in discrete regions of individual sensory, epithelia. The presence of multiple hair cell types in fishes provides strong support to the hypothesis of regional differences in the responses of individual otolithic sensory epithelia. The finding of hair cell types in fishes that closely resemble those found in amniote vestibular endorgans also suggests that hair cell heterogeneity arose earlier in the evolution of the vertebrate ear than previously thought.

  2. Generation of inner ear sensory cells from bone marrow-derived human mesenchymal stem cells.

    PubMed

    Durán Alonso, M Beatriz; Feijoo-Redondo, Ana; Conde de Felipe, Magnolia; Carnicero, Estela; García, Ana Sánchez; García-Sancho, Javier; Rivolta, Marcelo N; Giráldez, Fernando; Schimmang, Thomas

    2012-11-01

    Hearing loss is the most common sensory disorder in humans, its main cause being the loss of cochlear hair cells. We studied the potential of human mesenchymal stem cells (hMSCs) to differentiate towards hair cells and auditory neurons. hMSCs were first differentiated to neural progenitors and subsequently to hair cell- or auditory neuron-like cells using in vitro culture methods. Differentiation of hMSCs to an intermediate neural progenitor stage was critical for obtaining inner ear sensory lineages. hMSCs generated hair cell-like cells only when neural progenitors derived from nonadherent hMSC cultures grown in serum-free medium were exposed to EGF and retinoic acid. Auditory neuron-like cells were obtained when treated with retinoic acid, and in the presence of defined growth factor combinations containing Sonic Hedgehog. The results show the potential of hMSCs to give rise to inner ear sensory cells.

  3. Cell density and N-cadherin interactions regulate cell proliferation in the sensory epithelia of the inner ear.

    PubMed

    Warchol, Mark E

    2002-04-01

    Sensory hair cells in the inner ears of nonmammalian vertebrates can regenerate after injury. In many species, replacement hair cells are produced by the proliferation of epithelial supporting cells. Thus, the ability of supporting cells to undergo renewed proliferation is a key determinant of regenerative ability. The present study used cultures of isolated inner ear sensory epithelia to identify cellular signals that regulate supporting cell proliferation. Small pieces of sensory epithelia from the chicken utricle were cultured in glass microwells. Under those conditions, cell proliferation was inversely related to local cell density. The signaling molecules N-cadherin, beta-catenin, and focal adhesion kinase were immunolocalized in the cultured epithelial cells, and high levels of phosphotyrosine immunoreactivity were present at cell-cell junctions and focal contacts of proliferating cells. Binding of microbeads coated with a function-blocking antibody to N-cadherin inhibited ongoing proliferation. The growth of epithelial cells was also affected by the density of extracellular matrix molecules. The results suggest that cell density, cell-cell contact, and the composition of the extracellular matrix may be critical influences on the regulation of sensory regeneration in the inner ear.

  4. The molecular basis of neurosensory cell formation in ear development: a blueprint for hair cell and sensory neuron regeneration?

    PubMed Central

    Fritzsch, Bernd; Beisel, Kirk W.; Hansen, Laura

    2014-01-01

    Summary The inner ear of mammals uses neurosensory cells derived from the embryonic ear for mechanoelectric transduction of vestibular and auditory stimuli (the hair cells) and conducts this information to the brain via sensory neurons. As with most other neurons of mammals, lost hair cells and sensory neurons are not spontaneously replaced and result instead in age-dependent progressive hearing loss. We review the molecular basis of neurosensory development in the mouse ear to provide a blueprint for possible enhancement of therapeutically useful transformation of stem cells into lost neurosensory cells. We identify several readily available adult sources of stem cells that express, like the ectoderm-derived ear, genes known to be essential for ear development. Use of these stem cells combined with molecular insights into neurosensory cell specification and proliferation regulation of the ear, might allow for neurosensory regeneration of mammalian ears in the near future. PMID:17120192

  5. Artificial Induction of Sox21 Regulates Sensory Cell Formation in the Embryonic Chicken Inner Ear

    PubMed Central

    Freeman, Stephen D.; Daudet, Nicolas

    2012-01-01

    During embryonic development, hair cells and support cells in the sensory epithelia of the inner ear derive from progenitors that express Sox2, a member of the SoxB1 family of transcription factors. Sox2 is essential for sensory specification, but high levels of Sox2 expression appear to inhibit hair cell differentiation, suggesting that factors regulating Sox2 activity could be critical for both processes. Antagonistic interactions between SoxB1 and SoxB2 factors are known to regulate cell differentiation in neural tissue, which led us to investigate the potential roles of the SoxB2 member Sox21 during chicken inner ear development. Sox21 is normally expressed by sensory progenitors within vestibular and auditory regions of the early embryonic chicken inner ear. At later stages, Sox21 is differentially expressed in the vestibular and auditory organs. Sox21 is restricted to the support cell layer of the auditory epithelium, while it is enriched in the hair cell layer of the vestibular organs. To test Sox21 function, we used two temporally distinct gain-of-function approaches. Sustained over-expression of Sox21 from early developmental stages prevented prosensory specification, and abolished the formation of both hair cells and support cells. However, later induction of Sox21 expression at the time of hair cell formation in organotypic cultures of vestibular epithelia inhibited endogenous Sox2 expression and Notch activity, and biased progenitor cells towards a hair cell fate. Interestingly, Sox21 did not promote hair cell differentiation in the immature auditory epithelium, which fits with the expression of endogenous Sox21 within mature support cells in this tissue. These results suggest that interactions among endogenous SoxB family transcription factors may regulate sensory cell formation in the inner ear, but in a context-dependent manner. PMID:23071561

  6. Neurogenin 1 Null Mutant Ears Develop Fewer, Morphologically Normal Hair Cells in Smaller Sensory Epithelia Devoid of Innervation

    PubMed Central

    Ma, Qiufu; Anderson, David J.

    2000-01-01

    The proneuronal gene neurogenin 1 (ngn1) is essential for development of the inner-ear sensory neurons that are completely absent in ngn1 null mutants. Neither afferent, efferent, nor autonomic nerve fibers were detected in the ears of ngn1 null mutants. We suggest that efferent and autonomic fibers are lost secondarily to the absence of afferents. In this article we show that ngn1 null mutants develop smaller sensory epithelia with morphologically normal hair cells. In particular, the saccule is reduced dramatically and forms only a small recess with few hair cells along a duct connecting the utricle with the cochlea. Hair cells of newborn ngn1 null mutants show no structural abnormalities, suggesting that embryonic development of hair cells is independent of innervation. However, the less regular pattern of dispersal within sensory epithelia may be caused by some effects of afferents or to the stunted growth of the sensory epithelia. Tracing of facial and stato-acoustic nerves in control and ngn1 null mutants showed that only the distal, epibranchial, placode-derived sensory neurons of the geniculate ganglion exist in mutants. Tracing further showed that these geniculate ganglion neurons project exclusively to the solitary tract. In addition to the normal complement of facial branchial and visceral motoneurons, ngn1 null mutants have some trigeminal motoneurons and contralateral inner-ear efferents projecting, at least temporarily, through the facial nerve. These data suggest that some neurons in the brainstem (e.g., inner-ear efferents, trigeminal motoneurons) require afferents to grow along and redirect to ectopic cranial nerve roots in the absence of their corresponding sensory roots. PMID:11545141

  7. MEKK4 Signaling Regulates Sensory Cell Development and Function in the Mouse Inner Ear

    PubMed Central

    Haque, Khujista; Pandey, Atul K.; Zheng, Hong-Wei; Riazuddin, Saima; Sha, Su-Hua

    2016-01-01

    Mechanosensory hair cells (HCs) residing in the inner ear are critical for hearing and balance. Precise coordination of proliferation, sensory specification, and differentiation during development is essential to ensure the correct patterning of HCs in the cochlear and vestibular epithelium. Recent studies have revealed that FGF20 signaling is vital for proper HC differentiation. However, the mechanisms by which FGF20 signaling promotes HC differentiation remain unknown. Here, we show that mitogen-activated protein 3 kinase 4 (MEKK4) expression is highly regulated during inner ear development and is critical to normal cytoarchitecture and function. Mice homozygous for a kinase-inactive MEKK4 mutation exhibit significant hearing loss. Lack of MEKK4 activity in vivo also leads to a significant reduction in the number of cochlear and vestibular HCs, suggesting that MEKK4 activity is essential for overall development of HCs within the inner ear. Furthermore, we show that loss of FGF20 signaling in vivo inhibits MEKK4 activity, whereas gain of Fgf20 function stimulates MEKK4 expression, suggesting that Fgf20 modulates MEKK4 activity to regulate cellular differentiation. Finally, we demonstrate, for the first time, that MEKK4 acts as a critical node to integrate FGF20-FGFR1 signaling responses to specifically influence HC development and that FGFR1 signaling through activation of MEKK4 is necessary for outer hair cell differentiation. Collectively, this study provides compelling evidence of an essential role for MEKK4 in inner ear morphogenesis and identifies the requirement of MEKK4 expression in regulating the specific response of FGFR1 during HC development and FGF20/FGFR1 signaling activated MEKK4 for normal sensory cell differentiation. SIGNIFICANCE STATEMENT Sensory hair cells (HCs) are the mechanoreceptors within the inner ear responsible for our sense of hearing. HCs are formed before birth, and mammals lack the ability to restore the sensory deficits associated

  8. Gross and fine dissection of inner ear sensory epithelia in adult zebrafish (Danio rerio).

    PubMed

    Liang, Jin; Burgess, Shawn M

    2009-05-08

    Neurosensory epithelia in the inner ear are the crucial structures for hearing and balance functions. Therefore, it is important to understand the cellular and molecular features of the epithelia, which are mainly composed of two types of cells: hair cells (HCs) and supporting cells (SCs). Here we choose to study the inner ear sensory epithelia in adult zebrafish not only because the epithelial structures are highly conserved in all vertebrates studied, but also because the adult zebrafish is able to regenerate HCs, an ability that mammals lose shortly after birth. We use the inner ear of adult zebrafish as a model system to study the mechanisms of inner ear HC regeneration in adult vertebrates that could be helpful for clinical therapy of hearing/balance deficits in human as a result of HC loss. Here we demonstrate how to do gross and fine dissections of inner ear sensory epithelia in adult zebrafish. The gross dissection removes the tissues surrounding the inner ear and is helpful for preparing tissue sections, which allows us to examine the detailed structure of the sensory epithelia. The fine dissection cleans up the non-sensory-epithelial tissues of each individual epithelium and enables us to examine the heterogeneity of the whole epithelium easily in whole-mount epithelial samples.

  9. NOTCH SIGNALING ALTERS SENSORY OR NEURONAL CELL FATE SPECIFICATION OF INNER EAR STEM CELLS

    PubMed Central

    Jeon, Sang-Jun; Fujioka, Masato; Kim, Shi-Chan; Edge, Albert S.B.

    2011-01-01

    Multipotent progenitor cells in the otic placode give rise to the specialized cell types of the inner ear, including neurons, supporting cells and hair cells. The mechanisms governing acquisition of specific fates by the cells that form the cochleovestibular organs remain poorly characterized. Here we show that whereas blocking Notch signaling with a γ-secretase inhibitor increased the conversion of inner ear stem cells to hair cells by a mechanism that involved the upregulation of bHLH transcription factor, Math1 (mouse Atoh1), differentiation to a neuronal lineage was increased by expression of the Notch intracellular domain. The shift to a neuronal lineage could be attributed in part to the continued cell proliferation in cells that did not undergo sensory cell differentiation due to the high Notch signaling, but also involved upregulation of Ngn1. The Notch intracellular domain influenced Ngn1 indirectly by upregulation of Sox2, a transcription factor expressed in many neural progenitor cells, and directly by an interaction with an RBP-J binding site in the Ngn1 promoter/enhancer. The induction of Ngn1 was blocked partially by mutation of the RBP-J site and nearly completely when the mutation was combined with inhibition of Sox2 expression. Thus Notch signaling had a significant role in the fate specification of neurons and hair cells from inner ear stem cells, and decisions about cell fate were mediated in part by a differential effect of combinatorial signaling by Notch and Sox2 on the expression of bHLH transcription factors. PMID:21653840

  10. Concise review: Inner ear stem cells--an oxymoron, but why?

    PubMed

    Ronaghi, Mohammad; Nasr, Marjan; Heller, Stefan

    2012-01-01

    Hearing loss, caused by irreversible loss of cochlear sensory hair cells, affects millions of patients worldwide. In this concise review, we examine the conundrum of inner ear stem cells, which obviously are present in the inner ear sensory epithelia of nonmammalian vertebrates, giving these ears the ability to functionally recover even from repetitive ototoxic insults. Despite the inability of the mammalian inner ear to regenerate lost hair cells, there is evidence for cells with regenerative capacity because stem cells can be isolated from vestibular sensory epithelia and from the neonatal cochlea. Challenges and recent progress toward identification of the intrinsic and extrinsic signaling pathways that could be used to re-establish stemness in the mammalian organ of Corti are discussed. Copyright © 2011 AlphaMed Press.

  11. Generation of inner ear organoids containing functional hair cells from human pluripotent stem cells.

    PubMed

    Koehler, Karl R; Nie, Jing; Longworth-Mills, Emma; Liu, Xiao-Ping; Lee, Jiyoon; Holt, Jeffrey R; Hashino, Eri

    2017-06-01

    The derivation of human inner ear tissue from pluripotent stem cells would enable in vitro screening of drug candidates for the treatment of hearing and balance dysfunction and may provide a source of cells for cell-based therapies of the inner ear. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and WNT signaling to generate multiple otic-vesicle-like structures from a single stem-cell aggregate. Over 2 months, the vesicles develop into inner ear organoids with sensory epithelia that are innervated by sensory neurons. Additionally, using CRISPR-Cas9, we generate an ATOH1-2A-eGFP cell line to detect hair cell induction and demonstrate that derived hair cells exhibit electrophysiological properties similar to those of native sensory hair cells. Our culture system should facilitate the study of human inner ear development and research on therapies for diseases of the inner ear.

  12. BONE MARROW MESENCHYMAL STEM CELLS ARE PROGENITORS IN VITRO FOR INNER EAR HAIR CELLS

    PubMed Central

    Jeon, Sang-Jun; Oshima, Kazuo; Heller, Stefan; Edge, Albert S.B.

    2011-01-01

    Stem cells have been demonstrated in the inner ear but they do not spontaneously divide to replace damaged sensory cells. Mesenchymal stem cells (MSC) from bone marrow have been reported to differentiate into multiple lineages including neurons, and we therefore asked whether MSCs could generate sensory cells. Overexpression of the prosensory transcription factor, Math1, in sensory epithelial precursor cells induced expression of myosin VIIa, espin, Brn3c, p27Kip, and jagged2, indicating differentiation to inner ear sensory cells. Some of the cells displayed F-actin positive protrusions in the morphology characteristic of hair cell stereociliary bundles. Hair cell markers were also induced by culture of mouse MSC-derived cells in contact with embryonic chick inner ear cells, and this induction was not due to a cell fusion event, because the chick hair cells could be identified with a chick-specific antibody and chick and mouse antigens were never found in the same cell. PMID:17113786

  13. SENSORY HAIR CELL REGENERATION IN THE ZEBRAFISH LATERAL LINE

    PubMed Central

    Lush, Mark E.; Piotrowski, Tatjana

    2014-01-01

    Damage or destruction of sensory hair cells in the inner ear leads to hearing or balance deficits that can be debilitating, especially in older adults. Unfortunately, the damage is permanent, as regeneration of the inner ear sensory epithelia does not occur in mammals. Zebrafish and other non-mammalian vertebrates have the remarkable ability to regenerate sensory hair cells and understanding the molecular and cellular basis for this regenerative ability will hopefully aid us in designing therapies to induce regeneration in mammals. Zebrafish not only possess hair cells in the ear but also in the sensory lateral line system. Hair cells in both organs are functionally analogous to hair cells in the inner ear of mammals. The lateral line is a mechanosensory system found in most aquatic vertebrates that detects water motion and aids in predator avoidance, prey capture, schooling and mating. Although hair cell regeneration occurs in both the ear and lateral line, most research to date has focused on the lateral line due to its relatively simple structure and accessibility. Here we review the recent discoveries made during the characterization of hair cell regeneration in zebrafish. PMID:25045019

  14. Sensory hair cell regeneration in the zebrafish lateral line.

    PubMed

    Lush, Mark E; Piotrowski, Tatjana

    2014-10-01

    Damage or destruction of sensory hair cells in the inner ear leads to hearing or balance deficits that can be debilitating, especially in older adults. Unfortunately, the damage is permanent, as regeneration of the inner ear sensory epithelia does not occur in mammals. Zebrafish and other non-mammalian vertebrates have the remarkable ability to regenerate sensory hair cells and understanding the molecular and cellular basis for this regenerative ability will hopefully aid us in designing therapies to induce regeneration in mammals. Zebrafish not only possess hair cells in the ear but also in the sensory lateral line system. Hair cells in both organs are functionally analogous to hair cells in the inner ear of mammals. The lateral line is a mechanosensory system found in most aquatic vertebrates that detects water motion and aids in predator avoidance, prey capture, schooling, and mating. Although hair cell regeneration occurs in both the ear and lateral line, most research to date has focused on the lateral line due to its relatively simple structure and accessibility. Here we review the recent discoveries made during the characterization of hair cell regeneration in zebrafish. Copyright © 2014 Wiley Periodicals, Inc.

  15. Isolation of sphere-forming stem cells from the mouse inner ear.

    PubMed

    Oshima, Kazuo; Senn, Pascal; Heller, Stefan

    2009-01-01

    The mammalian inner ear has very limited ability to regenerate lost sensory hair cells. This deficiency becomes apparent when hair cell loss leads to hearing loss as a result of either ototoxic insult or the aging process. Coincidently, with this inability to regenerate lost hair cells, the adult cochlea does not appear to harbor cells with a proliferative capacity that could serve as progenitor cells for lost cells. In contrast, adult mammalian vestibular sensory epithelia display a limited ability for hair cell regeneration, and sphere-forming cells with stem cell features can be isolated from the adult murine vestibular system. The neonatal inner ear, however, does harbor sphere-forming stem cells residing in cochlear and vestibular tissues. Here, we provide protocols to isolate sphere-forming stem cells from neonatal vestibular and cochlear sensory epithelia as well as from the spiral ganglion. We further describe procedures for sphere propagation, cell differentiation, and characterization of inner ear cell types derived from spheres. Sphere-forming stem cells from the mouse inner ear are an important tool for the development of cellular replacement strategies of damaged inner ears and are a bona fide progenitor cell source for transplantation studies.

  16. Stem Cell Therapy for the Inner Ear

    PubMed Central

    Okano, Takayuki

    2012-01-01

    In vertebrates, perception of sound, motion, and balance is mediated through mechanosensory hair cells located within the inner ear. In mammals, hair cells are only generated during a short period of embryonic development. As a result, loss of hair cells as a consequence of injury, disease, or genetic mutation, leads to permanent sensory deficits. At present, cochlear implantation is the only option for profound hearing loss. However, outcomes are still variable and even the best implant cannot provide the acuity of a biological ear. The recent emergence of stem cell technology has the potential to open new approaches for hair cell regeneration. The goal of this review is to summarize the current state of inner ear stem cell research from a viewpoint of its clinical application for inner ear disorders to illustrate how complementary studies have the potential to promote and refine stem cell therapies for inner ear diseases. The review initially discusses our current understanding of the genetic pathways that regulate hair cell formation from inner ear progenitors during normal development. Subsequent sections discuss the possible use of endogenous inner ear stem cells to induce repair as well as the initial studies aimed at transplanting stem cells into the ear. PMID:22514095

  17. Cisplatin ototoxicity blocks sensory regeneration in the avian inner ear.

    PubMed

    Slattery, Eric L; Warchol, Mark E

    2010-03-03

    Cisplatin is a chemotherapeutic agent that is widely used in the treatment of solid tumors. Ototoxicity is a common side effect of cisplatin therapy and often leads to permanent hearing loss. The sensory organs of the avian ear are able to regenerate hair cells after aminoglycoside ototoxicity. This regenerative response is mediated by supporting cells, which serve as precursors to replacement hair cells. Given the antimitotic properties of cisplatin, we examined whether the avian ear was also capable of regeneration after cisplatin ototoxicity. Using cell and organ cultures of the chick cochlea and utricle, we found that cisplatin treatment caused apoptosis of both auditory and vestibular hair cells. Hair cell death in the cochlea occurred in a unique pattern, progressing from the low-frequency (distal) region toward the high-frequency (proximal) region. We also found that cisplatin caused a dose-dependent reduction in the proliferation of cultured supporting cells as well as increased apoptosis in those cells. As a result, we observed no recovery of hair cells after ototoxic injury caused by cisplatin. Finally, we explored the potential for nonmitotic hair cell recovery via activation of Notch pathway signaling. Treatment with the gamma-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester failed to promote the direct transdifferentiation of supporting cells into hair cells in cisplatin-treated utricles. Taken together, our data show that cisplatin treatment causes maintained changes to inner ear supporting cells and severely impairs the ability of the avian ear to regenerate either via proliferation or by direct transdifferentiation.

  18. Expression of S100 beta in sensory and secretory cells of the vertebrate inner ear

    NASA Technical Reports Server (NTRS)

    Fermin, C. D.; Martin, D. S.

    1995-01-01

    We evaluated anti-S100 beta expression in the chick (Gallus domesticus) inner ear and determined that: 1) the monomer anti-S100 beta is expressed differentially in the vestibular and auditory perikarya; 2) expression of S100 beta in the afferent nerve terminals is time-related to synapse and myelin formation; 3) the expression of the dimer anti-S100 alpha alpha beta beta and monomer anti-S100 beta overlaps in most inner ear cell types. Most S100 alpha alpha beta beta positive cells express S100 beta, but S100 beta positive cells do not always express S100 alpha alpha beta beta. 4) the expression of S100 beta is diffused over the perikaryal cytoplasm and nuclei of the acoustic ganglia but is concentrated over the nuclei of the vestibular perikarya. 6) S100 beta is expressed in secretory cells, and it is co-localized with GABA in sensory cells. 7) Color thresholding objective quantitation indicates that the amount of S100 beta was higher (mean 22, SD +/- 4) at E19 than at E9 (mean 34, SD +/- 3) in afferent axons. 8) Moreover, S100 beta was unchanged between E11-E19 in the perikaryal cytoplasm, but did change over the nuclei. At E9, 74%, and at E21, 5% of vestibular perikarya were positive. The data suggest that S100 beta may be physically associated with neuronal and ionic controlling cells of the vertebrate inner ear, where it could provide a dual ionic and neurotrophic modulatory function.

  19. Shaping of inner ear sensory organs through antagonistic interactions between Notch signalling and Lmx1a

    PubMed Central

    Mann, Zoe F; Chen, Ziqi; Chrysostomou, Elena; Żak, Magdalena; Kang, Miso; Canden, Elachumee

    2017-01-01

    The mechanisms of formation of the distinct sensory organs of the inner ear and the non-sensory domains that separate them are still unclear. Here, we show that several sensory patches arise by progressive segregation from a common prosensory domain in the embryonic chicken and mouse otocyst. This process is regulated by mutually antagonistic signals: Notch signalling and Lmx1a. Notch-mediated lateral induction promotes prosensory fate. Some of the early Notch-active cells, however, are normally diverted from this fate and increasing lateral induction produces misshapen or fused sensory organs in the chick. Conversely Lmx1a (or cLmx1b in the chick) allows sensory organ segregation by antagonizing lateral induction and promoting commitment to the non-sensory fate. Our findings highlight the dynamic nature of sensory patch formation and the labile character of the sensory-competent progenitors, which could have facilitated the emergence of new inner ear organs and their functional diversification in the course of evolution. PMID:29199954

  20. Otx1 null mutant mice show partial segregation of sensory epithelia comparable to lamprey ears

    NASA Technical Reports Server (NTRS)

    Fritzsch, B.; Signore, M.; Simeone, A.

    2001-01-01

    We investigated the development of inner ear innervation in Otx1 null mutants, which lack a horizontal canal, between embryonic day 12 (E12) and postnatal day 7 (P7) with DiI and immunostaining for acetylated tubulin. Comparable to control animals, horizontal crista-like fibers were found to cross over the utricle in Otx1 null mice. In mutants these fibers extend toward an area near the endolymphatic duct, not to a horizontal crista. Most Otx1 null mutants had a small patch of sensory hair cells at this position. Measurement of the area of the utricular macula suggested it to be enlarged in Otx1 null mutants. We suggest that parts of the horizontal canal crista remain incorporated in the utricular sensory epithelium in Otx1 null mutants. Other parts of the horizontal crista appear to be variably segregated to form the isolated patch of hair cells identifiable by the unique fiber trajectory as representing the horizontal canal crista. Comparison with lamprey ear innervation reveals similarities in the pattern of innervation with the dorsal macula, a sensory patch of unknown function. SEM data confirm that all foramina are less constricted in Otx1 null mutants. We propose that Otx1 is not directly involved in sensory hair cell formation of the horizontal canal but affects the segregation of the horizontal canal crista from the utricle. It also affects constriction of the two main foramina in the ear, but not their initial formation. Otx1 is thus causally related to horizontal canal morphogenesis as well as morphogenesis of these foramina.

  1. Conditional Deletion of N-Myc Disrupts Neurosensory and Non-sensory Development of the Ear

    PubMed Central

    Kopecky, Benjamin; Santi, Peter; Johnson, Shane; Schmitz, Heather; Fritzsch, Bernd

    2011-01-01

    Ear development requires interactions of transcription factors for proliferation and differentiation. The proto-oncogene N-Myc is a member of the Myc family that regulate proliferation. To investigate the function of N-Myc, we conditionally knocked out N-Myc in the ear using Tg(Pax2-Cre) and Foxg 1KiCre. N-Myc CKOs had reduced growth of the ear, abnormal morphology including fused sensory epithelia, disrupted histology, and disorganized neuronal innervation. Using Thin-Sheet Laser Imaging Microscopy (TSLIM), 3D reconstruction and quantification of the cochlea revealed a greater than fifty percent size reduction. Immunochemistry and in situ hybridization showed a gravistatic organ-cochlear fusion and a “circularized” apex with no clear inner and outer hair cells. Furthermore, the abnormally developed cochlea had cross innervation from the vestibular ganglion near the basal tip. These findings are put in the context of the possible functional relationship of N-Myc with a number of other cell proliferative and fate determining genes during ear development. PMID:21448975

  2. Insights into inner ear-specific gene regulation: epigenetics and non-coding RNAs in inner ear development and regeneration

    PubMed Central

    Avraham, Karen B.

    2016-01-01

    The vertebrate inner ear houses highly specialized sensory organs, tuned to detect and encode sound, head motion and gravity. Gene expression programs under the control of transcription factors orchestrate the formation and specialization of the non-sensory inner ear labyrinth and its sensory constituents. More recently, epigenetic factors and non-coding RNAs emerged as an additional layer of gene regulation, both in inner ear development and disease. In this review, we provide an overview on how epigenetic modifications and non-coding RNAs, in particular microRNAs (miRNAs), influence gene expression and summarize recent discoveries that highlight their critical role in the proper formation of the inner ear labyrinth and its sensory organs. In contrast to non-mammalian vertebrates, adult mammals lack the ability to regenerate inner ear mechano-sensory hair cells. Finally, we discuss recent insights into how epigenetic factors and miRNAs may facilitate, or in the case of mammals, restrict sensory hair cell regeneration. PMID:27836639

  3. A review of gene delivery and stem cell based therapies for regenerating inner ear hair cells.

    PubMed

    Devarajan, Keerthana; Staecker, Hinrich; Detamore, Michael S

    2011-09-13

    Sensory neural hearing loss and vestibular dysfunction have become the most common forms of sensory defects, affecting millions of people worldwide. Developing effective therapies to restore hearing loss is challenging, owing to the limited regenerative capacity of the inner ear hair cells. With recent advances in understanding the developmental biology of mammalian and non-mammalian hair cells a variety of strategies have emerged to restore lost hair cells are being developed. Two predominant strategies have developed to restore hair cells: transfer of genes responsible for hair cell genesis and replacement of missing cells via transfer of stem cells. In this review article, we evaluate the use of several genes involved in hair cell regeneration, the advantages and disadvantages of the different viral vectors employed in inner ear gene delivery and the insights gained from the use of embryonic, adult and induced pluripotent stem cells in generating inner ear hair cells. Understanding the role of genes, vectors and stem cells in therapeutic strategies led us to explore potential solutions to overcome the limitations associated with their use in hair cell regeneration.

  4. Development of inner ear afferent connections: forming primary neurons and connecting them to the developing sensory epithelia

    NASA Technical Reports Server (NTRS)

    Fritzsch, Bernd

    2003-01-01

    The molecular and cellular origin of the primary neurons of the inner ear, the vestibular and spiral neurons, is reviewed including how they connect to the specific sensory epithelia and what the molecular nature of their survival is. Primary neurons of the ear depend on a single basic Helix-Loop-Helix (bHLH) protein for their formation, neurogenin 1 (ngn1). An immediate downstream gene is the bHLH gene neuronal differentiation (NeuroD). Targeted null mutations of ngn1 results in absence of primary neuron formation; targeted null mutation of NeuroD results in loss of almost all spiral and many vestibular neurons. NeuroD and a later expressed gene, Brn3a, play a role in pathfinding to and within sensory epithelia. The molecular nature of this pathfinding property is unknown. Reduction of hair cells in ngn1 null mutations suggests a clonal relationship with primary neurons. This relationship may play some role in specifying the identity of hair cells and the primary neurons that connect with them. Primary neuron neurites growth to sensory epithelia is initially independent of trophic factors released from developing sensory epithelia, but becomes rapidly dependent on those factors. Null mutations of specific neurotrophic factors lose distinct primary neuron populations which undergo rapid embryonic cell death.

  5. Vestibular sensory functional status of cochlear implanted ears versus non-implanted ears in bilateral profound deaf adults.

    PubMed

    Cozma, Romică Sebastian; Dima-Cozma, Lucia Corina; Rădulescu, Luminiţa Mihaela; Hera, Maria Cristina; Mârţu, Cristian; Olariu, Raluca; Cobzeanu, Bogdan Mihail; Bitere, Oana Roxana; Cobzeanu, Mihail Dan

    2018-01-01

    Patients with hearing loss who underwent cochlear implantation can present symptomatic or asymptomatic vestibular damages earlier or later after the surgery. The vestibular permanent lesions could be acute, produced by surgical trauma or could be progressive due to local morphological changes made by the presence of the portelectrode in the inner ear (fibrosis related, ossification, basilar membrane distortion, endolymphatic hydrops). Besides histopathological findings in inner ear of cochlear implanted patients, the vestibular permanent damages could be found by assessment of clinical vestibular status. This study reports the sensorial vestibular functional findings for adults in cochlear implanted ears related to the electrode insertion type (cochleostomy or round window approach) and comparing to non-implanted deaf ears. A total of 20 adult patients with 32 cochlear implanted ears (12 patients with binaural cochlear implant and eight with monoaural) were selected for postoperatory vestibular examination by cervical and ocular vestibular myogenic potentials and vestibular caloric tests. The same tests were made for a control group of 22 non-implanted deaf ears. Functional testing results were reported related to the electrode insertion approach. For the cochleostomy group, we found different deficits: in 40% for saccular function, 44% for utricular function, and 12% horizontal canal dysfunction. In round window group, the deficit was present in 14.29% for saccular function, 28.57% for utricular function, and 28.58% for horizontal canal. In 46.88% of implanted ears, the vestibular function was completely preserved on all tested sensors. In conclusion, the vestibular functional status after inner ear surgery presents sensorial damages in 53.12% ears compare with the vestibular dysfunction existing in 50% of deaf non-operated ears. Round window insertion allows for better conservation of the vestibular function.

  6. Sensory hair cell death and regeneration in fishes

    PubMed Central

    Monroe, Jerry D.; Rajadinakaran, Gopinath; Smith, Michael E.

    2015-01-01

    Sensory hair cells are specialized mechanotransductive receptors required for hearing and vestibular function. Loss of hair cells in humans and other mammals is permanent and causes reduced hearing and balance. In the early 1980’s, it was shown that hair cells continue to be added to the inner ear sensory epithelia in cartilaginous and bony fishes. Soon thereafter, hair cell regeneration was documented in the chick cochlea following acoustic trauma. Since then, research using chick and other avian models has led to great insights into hair cell death and regeneration. However, with the rise of the zebrafish as a model organism for studying disease and developmental processes, there has been an increased interest in studying sensory hair cell death and regeneration in its lateral line and inner ears. Advances derived from studies in zebrafish and other fish species include understanding the effect of ototoxins on hair cells and finding otoprotectants to mitigate ototoxin damage, the role of cellular proliferation vs. direct transdifferentiation during hair cell regeneration, and elucidating cellular pathways involved in the regeneration process. This review will summarize research on hair cell death and regeneration using fish models, indicate the potential strengths and weaknesses of these models, and discuss several emerging areas of future studies. PMID:25954154

  7. Distinct capacity for differentiation to inner ear cell types by progenitor cells of the cochlea and vestibular organs

    PubMed Central

    McLean, Will J.; McLean, Dalton T.; Eatock, Ruth Anne

    2016-01-01

    Disorders of hearing and balance are most commonly associated with damage to cochlear and vestibular hair cells or neurons. Although these cells are not capable of spontaneous regeneration, progenitor cells in the hearing and balance organs of the neonatal mammalian inner ear have the capacity to generate new hair cells after damage. To investigate whether these cells are restricted in their differentiation capacity, we assessed the phenotypes of differentiated progenitor cells isolated from three compartments of the mouse inner ear – the vestibular and cochlear sensory epithelia and the spiral ganglion – by measuring electrophysiological properties and gene expression. Lgr5+ progenitor cells from the sensory epithelia gave rise to hair cell-like cells, but not neurons or glial cells. Newly created hair cell-like cells had hair bundle proteins, synaptic proteins and membrane proteins characteristic of the compartment of origin. PLP1+ glial cells from the spiral ganglion were identified as neural progenitors, which gave rise to neurons, astrocytes and oligodendrocytes, but not hair cells. Thus, distinct progenitor populations from the neonatal inner ear differentiate to cell types associated with their organ of origin. PMID:27789624

  8. Adenovirus Vectors Target Several Cell Subtypes of Mammalian Inner Ear In Vivo

    PubMed Central

    Li, Wenyan; Shen, Jun

    2016-01-01

    Mammalian inner ear harbors diverse cell types that are essential for hearing and balance. Adenovirus is one of the major vectors to deliver genes into the inner ear for functional studies and hair cell regeneration. To identify adenovirus vectors that target specific cell subtypes in the inner ear, we studied three adenovirus vectors, carrying a reporter gene encoding green fluorescent protein (GFP) from two vendors or with a genome editing gene Cre recombinase (Cre), by injection into postnatal days 0 (P0) and 4 (P4) mouse cochlea through scala media by cochleostomy in vivo. We found three adenovirus vectors transduced mouse inner ear cells with different specificities and expression levels, depending on the type of adenoviral vectors and the age of mice. The most frequently targeted region was the cochlear sensory epithelium, including auditory hair cells and supporting cells. Adenovirus with GFP transduced utricular supporting cells as well. This study shows that adenovirus vectors are capable of efficiently and specifically transducing different cell types in the mammalian inner ear and provides useful tools to study inner ear gene function and to evaluate gene therapy to treat hearing loss and vestibular dysfunction. PMID:28116172

  9. Concise Review: Inner Ear Stem Cells—An Oxymoron, But Why?

    PubMed Central

    Ronaghi, Mohammad; Nasr, Marjan; Heller, Stefan

    2012-01-01

    Hearing loss, caused by irreversible loss of cochlear sensory hair cells, affects millions of patients worldwide. In this concise review, we examine the conundrum of inner ear stem cells, which obviously are present in the inner ear sensory epithelia of nonmammalian vertebrates, giving these ears the ability to functionally recover even from repetitive ototoxic insults. Despite the inability of the mammalian inner ear to regenerate lost hair cells, there is evidence for cells with regenerative capacity because stem cells can be isolated from vestibular sensory epithelia and from the neonatal cochlea. Challenges and recent progress toward identification of the intrinsic and extrinsic signaling pathways that could be used to re-establish stemness in the mammalian organ of Corti are discussed. PMID:22102534

  10. Zebrafish Foxi1 provides a neuronal ground state during inner ear induction preceding the Dlx3b/4b-regulated sensory lineage.

    PubMed

    Hans, Stefan; Irmscher, Anne; Brand, Michael

    2013-05-01

    Vertebrate inner ear development is a complex process that involves the induction of a common territory for otic and epibranchial precursors and their subsequent segregation into otic and epibranchial cell fates. In zebrafish, the otic-epibranchial progenitor domain (OEPD) is induced by Fgf signaling in a Foxi1- and Dlx3b/4b-dependent manner, but the functional differences of Foxi1 and Dlx3b/4b in subsequent cell fate specifications within the developing inner ear are poorly understood. Based on pioneer tracking (PioTrack), a novel Cre-dependent genetic lineage tracing method, and genetic data, we show that the competence to embark on a neuronal or sensory fate is provided sequentially and very early during otic placode induction. Loss of Foxi1 prevents neuronal precursor formation without affecting hair cell specification, whereas loss of Dlx3b/4b inhibits hair cell but not neuronal precursor formation. Consistently, in Dlx3b/4b- and Sox9a-deficient b380 mutants almost all otic epithelial fates are absent, including sensory hair cells, and the remaining otic cells adopt a neuronal fate. Furthermore, the progenitors of the anterior lateral line ganglia also arise from the OEPD in a Foxi1-dependent manner but are unaffected in the absence of Dlx3b/4b or in b380 mutants. Thus, in addition to otic fate Foxi1 provides neuronal competence during OEPD induction prior to and independently of the Dlx3b/4b-mediated sensory fate of the developing inner ear.

  11. Regulated reprogramming in the regeneration of sensory receptor cells

    PubMed Central

    Bermingham-McDonogh, Olivia; Reh, Thomas A.

    2015-01-01

    The sensory reception of vision, olfaction, hearing and balance are mediated by receptors that reside in specialized epithelial organs. Age-related degeneration of the photoreceptors in the retina and the hair cells in the cochlea, caused by macular degeneration and sensorineural hearing loss, respectively, affect a growing number of individuals. Although sensory receptor cells in the mammalian retina and inner ear show only limited or no regeneration, in many non-mammalian vertebrates, these sensory epithelia show remarkable regenerative potential. We summarize the current state of knowledge of regeneration in the specialized sense organs in both non-mammalian vertebrates and mammals, and discuss possible areas where new advances in regenerative medicine might provide approaches to successfully stimulate sensory receptor cell regeneration. The field of regenerative medicine is still in its infancy, but new approaches using stem cells and reprogramming suggest ways in which the potential for regeneration may be restored in individuals suffering from sensory loss. PMID:21835338

  12. Autonomous assembly of epithelial structures by subrenal implantation of dissociated embryonic inner-ear cells.

    PubMed

    Wang, Li; Zhang, Kaiqing; Zhu, Helen He; Gao, Wei-Qiang

    2015-05-27

    Microenvironment and cell-cell interactions play an important role during embryogenesis and are required for the stemness and differentiation of stem cells. The inner-ear sensory epithelium, containing hair cells and supporting cells, is derived from the stem cells within the otic vesicle at early embryonic stages. However, whether or not such microenvironment or cell-cell interactions within the embryonic otic tissue have the capacity to regulate the proliferation and differentiation of stem cells and to autonomously reassemble the cells into epithelial structures is unknown. Here, we report that on enzymatic digestion and dissociation to harvest all the single cells from 13.5-day-old rat embryonic (E13.5) inner-ear tissue as well as on implantation of these cells under renal capsules; the dissociated cells are able to reassemble themselves to form epithelial structures as early as 7 days after implantation. By 25 days after implantation, more mature epithelial structures are formed. Immunostaining with cell-type-specific markers reveals that hair cells and supporting cells are not only formed, but are also well aligned with the hair cells located in the apical layer surrounded by the supporting cells. These findings suggest that microenvironment and cell-cell interactions within the embryonic inner-ear tissue have the autonomous signals to induce the formation of sensory epithelial structures. This method may also provide a useful system to study the potential of stem cells to differentiate into hair cells in vivo.

  13. [Characterization of stem cells derived from the neonatal auditory sensory epithelium].

    PubMed

    Diensthuber, M; Heller, S

    2010-11-01

    In contrast to regenerating hair cell-bearing organs of nonmammalian vertebrates the adult mammalian organ of Corti appears to have lost its ability to maintain stem cells. The result is a lack of regenerative ability and irreversible hearing loss following auditory hair cell death. Unexpectedly, the neonatal auditory sensory epithelium has recently been shown to harbor cells with stem cell features. The origin of these cells within the cochlea's sensory epithelium is unknown. We applied a modified neurosphere assay to identify stem cells within distinct subregions of the neonatal mouse auditory sensory epithelium. Sphere cells were characterized by multiple markers and morphologic techniques. Our data reveal that both the greater and the lesser epithelial ridge contribute to the sphere-forming stem cell population derived from the auditory sensory epithelium. These self-renewing sphere cells express a variety of markers for neural and otic progenitor cells and mature inner ear cell types. Stem cells can be isolated from specific regions of the auditory sensory epithelium. The distinct features of these cells imply a potential application in the development of a cell replacement therapy to regenerate the damaged sensory epithelium.

  14. Segregating neural and mechanosensory fates in the developing ear: patterning, signaling, and transcriptional control

    PubMed Central

    Raft, Steven; Groves, Andrew K.

    2014-01-01

    The vertebrate inner ear is composed of multiple sensory receptor epithelia, each of which is specialized for detection of sound, gravity or angular acceleration. Each receptor epithelium contains mechanosensitive hair cells, which are connected to the brainstem by bipolar sensory neurons. Hair cells and their associated neurons are derived from the embryonic rudiment of the inner ear epithelium, but the precise spatial and temporal patterns of their generation, as well as the signals that coordinate these events, have only recently begun to be understood. Gene expression, lineage tracing, and mutant analyses suggest that both neurons and hair cells are generated from a common domain of neural and sensory competence in the embryonic inner ear rudiment. Members of the Shh, Wnt and FGF families, together with retinoic acid signals, regulate transcription factor genes within the inner ear rudiment to establish the axial identity of the ear and regionalize neurogenic activity. Close-range signaling, such as that of the Notch pathway, specifies the fate of sensory regions and individual cell types. We also describe positive and negative interactions between basic helix-loop-helix and SoxB family transcription factors that specify either neuronal or sensory fates in a context-dependent manner. Finally, we review recent work on inner ear development in zebrafish, which demonstrates that the relative timing of neurogenesis and sensory epithelial formation is not phylogenetically constrained. PMID:24902666

  15. Evolution of vertebrate mechanosensory hair cells and inner ears: toward identifying stimuli that select mutation driven altered morphologies

    PubMed Central

    Fritzsch, Bernd; Straka, Hans

    2014-01-01

    Among the major distance senses of vertebrates, the ear is unique in its complex morphological changes during evolution. Conceivably, these changes enable the ear to adapt toward sensing various physically well-characterized stimuli. This review develops a scenario that integrates sensory cell with organ evolution. We propose that molecular and cellular evolution of the vertebrate hair cells occurred prior to the formation of the vertebrate ear. We previously proposed that the genes driving hair cell differentiation, were aggregated in the otic region through developmental re-patterning that generated a unique vertebrate embryonic structure, the otic placode. In agreement with the presence of graviceptive receptors in many vertebrate outgroups, it is likely that the vertebrate ear originally functioned as a simple gravity-sensing organ. Based on the rare occurrence of angular acceleration receptors in vertebrate outgroups, we further propose that the canal system evolved with a more sophisticated ear morphogenesis. This evolving morphogenesis obviously turned the initial otocyst into a complex set of canals and recesses, harboring multiple sensory epithelia each adapted to the acquisition of a specific aspect of a given physical stimulus. As support for this evolutionary progression, we provide several details of the molecular basis of ear development. PMID:24281353

  16. Shaping sound in space: the regulation of inner ear patterning.

    PubMed

    Groves, Andrew K; Fekete, Donna M

    2012-01-01

    The inner ear is one of the most morphologically elaborate tissues in vertebrates, containing a group of mechanosensitive sensory organs that mediate hearing and balance. These organs are arranged precisely in space and contain intricately patterned sensory epithelia. Here, we review recent studies of inner ear development and patterning which reveal that multiple stages of ear development - ranging from its early induction from the embryonic ectoderm to the establishment of the three cardinal axes and the fine-grained arrangement of sensory cells - are orchestrated by gradients of signaling molecules.

  17. Shaping sound in space: the regulation of inner ear patterning

    PubMed Central

    Groves, Andrew K.; Fekete, Donna M.

    2012-01-01

    The inner ear is one of the most morphologically elaborate tissues in vertebrates, containing a group of mechanosensitive sensory organs that mediate hearing and balance. These organs are arranged precisely in space and contain intricately patterned sensory epithelia. Here, we review recent studies of inner ear development and patterning which reveal that multiple stages of ear development – ranging from its early induction from the embryonic ectoderm to the establishment of the three cardinal axes and the fine-grained arrangement of sensory cells – are orchestrated by gradients of signaling molecules. PMID:22186725

  18. A simple method for purification of vestibular hair cells and non-sensory cells, and application for proteomic analysis.

    PubMed

    Herget, Meike; Scheibinger, Mirko; Guo, Zhaohua; Jan, Taha A; Adams, Christopher M; Cheng, Alan G; Heller, Stefan

    2013-01-01

    Mechanosensitive hair cells and supporting cells comprise the sensory epithelia of the inner ear. The paucity of both cell types has hampered molecular and cell biological studies, which often require large quantities of purified cells. Here, we report a strategy allowing the enrichment of relatively pure populations of vestibular hair cells and non-sensory cells including supporting cells. We utilized specific uptake of fluorescent styryl dyes for labeling of hair cells. Enzymatic isolation and flow cytometry was used to generate pure populations of sensory hair cells and non-sensory cells. We applied mass spectrometry to perform a qualitative high-resolution analysis of the proteomic makeup of both the hair cell and non-sensory cell populations. Our conservative analysis identified more than 600 proteins with a false discovery rate of <3% at the protein level and <1% at the peptide level. Analysis of proteins exclusively detected in either population revealed 64 proteins that were specific to hair cells and 103 proteins that were only detectable in non-sensory cells. Statistical analyses extended these groups by 53 proteins that are strongly upregulated in hair cells versus non-sensory cells and vice versa by 68 proteins. Our results demonstrate that enzymatic dissociation of styryl dye-labeled sensory hair cells and non-sensory cells is a valid method to generate pure enough cell populations for flow cytometry and subsequent molecular analyses.

  19. Epigenetic influences on sensory regeneration: histone deacetylases regulate supporting cell proliferation in the avian utricle.

    PubMed

    Slattery, Eric L; Speck, Judith D; Warchol, Mark E

    2009-09-01

    The sensory hair cells of the cochlea and vestibular organs are essential for normal hearing and balance function. The mammalian ear possesses a very limited ability to regenerate hair cells and their loss can lead to permanent sensory impairment. In contrast, hair cells in the avian ear are quickly regenerated after acoustic trauma or ototoxic injury. The very different regenerative abilities of the avian vs. mammalian ear can be attributed to differences in injury-evoked expression of genes that either promote or inhibit the production of new hair cells. Gene expression is regulated both by the binding of cis-regulatory molecules to promoter regions as well as through structural modifications of chromatin (e.g., methylation and acetylation). This study examined effects of histone deacetylases (HDACs), whose main function is to modify histone acetylation, on the regulation of regenerative proliferation in the chick utricle. Cultures of regenerating utricles and dissociated cells from the utricular sensory epithelia were treated with the HDAC inhibitors valproic acid, trichostatin A, sodium butyrate, and MS-275. All of these molecules prevent the enzymatic removal of acetyl groups from histones, thus maintaining nuclear chromatin in a "relaxed" (open) configuration. Treatment with all inhibitors resulted in comparable decreases in supporting cell proliferation. We also observed that treatment with the HDAC1-, 2-, and 3-specific inhibitor MS-275 was sufficient to reduce proliferation and that two class I HDACs--HDAC1 and HDAC2--were expressed in the sensory epithelium of the utricle. These results suggest that inhibition of specific type I HDACs is sufficient to prevent cell cycle entry in supporting cells. Notably, treatment with HDAC inhibitors did not affect the differentiation of replacement hair cells. We conclude that histone deacetylation is a positive regulator of regenerative proliferation but is not critical for avian hair cell differentiation.

  20. Adipose-derived stromal cells enhance auditory neuron survival in an animal model of sensory hearing loss.

    PubMed

    Schendzielorz, Philipp; Vollmer, Maike; Rak, Kristen; Wiegner, Armin; Nada, Nashwa; Radeloff, Katrin; Hagen, Rudolf; Radeloff, Andreas

    2017-10-01

    A cochlear implant (CI) is an electronic prosthesis that can partially restore speech perception capabilities. Optimum information transfer from the cochlea to the central auditory system requires a proper functioning auditory nerve (AN) that is electrically stimulated by the device. In deafness, the lack of neurotrophic support, normally provided by the sensory cells of the inner ear, however, leads to gradual degeneration of auditory neurons with undesirable consequences for CI performance. We evaluated the potential of adipose-derived stromal cells (ASCs) that are known to produce neurotrophic factors to prevent neural degeneration in sensory hearing loss. For this, co-cultures of ASCs with auditory neurons have been studied, and autologous ASC transplantation has been performed in a guinea pig model of gentamicin-induced sensory hearing loss. In vitro ASCs were neuroprotective and considerably increased the neuritogenesis of auditory neurons. In vivo transplantation of ASCs into the scala tympani resulted in an enhanced survival of auditory neurons. Specifically, peripheral AN processes that are assumed to be the optimal activation site for CI stimulation and that are particularly vulnerable to hair cell loss showed a significantly higher survival rate in ASC-treated ears. ASC transplantation into the inner ear may restore neurotrophic support in sensory hearing loss and may help to improve CI performance by enhanced AN survival. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  1. Inner Ear Drug Delivery for Auditory Applications

    PubMed Central

    Swan, Erin E. Leary; Mescher, Mark J.; Sewell, William F.; Tao, Sarah L.; Borenstein, Jeffrey T.

    2008-01-01

    Many inner ear disorders cannot be adequately treated by systemic drug delivery. A blood-cochlear barrier exists, similar physiologically to the blood-brain barrier, which limits the concentration and size of molecules able to leave the circulation and gain access to the cells of the inner ear. However, research in novel therapeutics and delivery systems has led to significant progress in the development of local methods of drug delivery to the inner ear. Intratympanic approaches, which deliver therapeutics to the middle ear, rely on permeation through tissue for access to the structures of the inner ear, whereas intracochlear methods are able to directly insert drugs into the inner ear. Innovative drug delivery systems to treat various inner ear ailments such as ototoxicity, sudden sensorineural hearing loss, autoimmune inner ear disease, and for preserving neurons and regenerating sensory cells are being explored. PMID:18848590

  2. Maintained expression of the planar cell polarity molecule Vangl2 and reformation of hair cell orientation in the regenerating inner ear.

    PubMed

    Warchol, Mark E; Montcouquiol, Mireille

    2010-09-01

    The avian inner ear possesses a remarkable ability to regenerate sensory hair cells after ototoxic injury. Regenerated hair cells possess phenotypes and innervation that are similar to those found in the undamaged ear, but little is known about the signaling pathways that guide hair cell differentiation during the regenerative process. The aim of the present study was to examine the factors that specify the orientation of hair cell stereocilia bundles during regeneration. Using organ cultures of the chick utricle, we show that hair cells are properly oriented after having regenerated entirely in vitro and that orientation is not affected by surgical removal of the striolar reversal zone. These results suggest that the orientation of regenerating stereocilia is not guided by the release of a diffusible morphogen from the striolar reversal zone but is specified locally within the regenerating sensory organ. In order to determine the nature of the reorientation cues, we examined the expression patterns of the core planar cell polarity molecule Vangl2 in the normal and regenerating utricle. We found that Vangl2 is asymmetrically expressed on cells within the sensory epithelium and that this expression pattern is maintained after ototoxic injury and throughout regeneration. Notably, treatment with a small molecule inhibitor of c-Jun-N-terminal kinase disrupted the orientation of regenerated hair cells. Both of these results are consistent with the hypothesis that noncanonical Wnt signaling guides hair cell orientation during regeneration.

  3. Developmental evolutionary biology of the vertebrate ear: conserving mechanoelectric transduction and developmental pathways in diverging morphologies

    NASA Technical Reports Server (NTRS)

    Fritzsch, B.; Beisel, K. W.; Bermingham, N. A.

    2000-01-01

    This brief overview shows that a start has been made to molecularly dissect vertebrate ear development and its evolutionary conservation to the development of the insect hearing organ. However, neither the patterning process of the ear nor the patterning process of insect sensory organs is sufficiently known at the moment to provide more than a first glimpse. Moreover, hardly anything is known about otocyst development of the cephalopod molluscs, another triploblast lineage that evolved complex 'ears'. We hope that the apparent conserved functional and cellular components present in the ciliated sensory neurons/hair cells will also be found in the genes required for vertebrate ear and insect sensory organ morphogenesis (Fig. 3). Likewise, we expect that homologous pre-patterning genes will soon be identified for the non-sensory cell development, which is more than a blocking of neuronal development through the Delta/Notch signaling system. Generation of the apparently unique ear could thus represent a multiplication of non-sensory cells by asymmetric and symmetric divisions as well as modification of existing patterning process by implementing novel developmental modules. In the final analysis, the vertebrate ear may come about by increasing the level of gene interactions in an already existing and highly conserved interactive cascade of bHLH genes. Since this was apparently achieved in all three lineages of triploblasts independently (Fig. 3), we now need to understand how much of the morphogenetic cascades are equally conserved across phyla to generate complex ears. The existing mutations in humans and mice may be able to point the direction of future research to understand the development of specific cell types and morphologies in the formation of complex arthropod, cephalopod, and vertebrate 'ears'.

  4. Identification of Adeno-Associated Viral Vectors That Target Neonatal and Adult Mammalian Inner Ear Cell Subtypes

    PubMed Central

    Shu, Yilai; Tao, Yong; Wang, Zhengmin; Tang, Yong; Li, Huawei; Dai, Pu; Gao, Guangping; Chen, Zheng-Yi

    2016-01-01

    The mammalian inner ear consists of diverse cell types with important functions. Gene mutations in these diverse cell types have been found to underlie different forms of genetic hearing loss. Targeting these mutations for gene therapy development represents a future therapeutic strategy to treat hearing loss. Adeno-associated viral (AAV) vectors have become the vector of choice for gene delivery in animal models in vivo. To identify AAV vectors that target inner ear cell subtypes, we systemically screened 12 AAV vectors with different serotypes (AAV1, 2, 5, 6, 6.2, 7, 8, 9, rh.8, rh.10, rh.39, and rh.43) that carry a reporter gene GFP in neonatal and adult mice by microinjection in vivo. We found that most AAVs infect both neonatal and adult inner ear, with different specificities and expression levels. The inner ear cochlear sensory epithelial region, which includes auditory hair cells and supporting cells, is most frequently targeted for gene delivery. Expression of the transgene is sustained, and neonatal inner ear delivery does not adversely affect hearing. Adult inner ear injection of AAV has a similar infection pattern as the younger inner ear, with the exception that outer hair cell death caused by the injection procedure can lead to hearing loss. In the adult, more so than in the neonatal mice, cell types infected and efficiency of infection are correlated with the site of injection. Most infected cells survive in neonatal and adult inner ears. The study adds to the list of AAV vectors that transduce the mammalian inner ear efficiently, providing the tools that are important to study inner ear gene function and for the development of gene therapy to treat hearing loss. PMID:27342665

  5. The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival

    NASA Technical Reports Server (NTRS)

    Wallis, Deeann; Hamblen, Melanie; Zhou, Yi; Venken, Koen J T.; Schumacher, Armin; Grimes, H. Leighton; Zoghbi, Huda Y.; Orkin, Stuart H.; Bellen, Hugo J.

    2003-01-01

    Gfi1 was first identified as causing interleukin 2-independent growth in T cells and lymphomagenesis in mice. Much work has shown that Gfi1 and Gfi1b, a second mouse homolog, play pivotal roles in blood cell lineage differentiation. However, neither Gfi1 nor Gfi1b has been implicated in nervous system development, even though their invertebrate homologues, senseless in Drosophila and pag-3 in C. elegans are expressed and required in the nervous system. We show that Gfi1 mRNA is expressed in many areas that give rise to neuronal cells during embryonic development in mouse, and that Gfi1 protein has a more restricted expression pattern. By E12.5 Gfi1 mRNA is expressed in both the CNS and PNS as well as in many sensory epithelia including the developing inner ear epithelia. At later developmental stages, Gfi1 expression in the ear is refined to the hair cells and neurons throughout the inner ear. Gfi1 protein is expressed in a more restricted pattern in specialized sensory cells of the PNS, including the eye, presumptive Merkel cells, the lung and hair cells of the inner ear. Gfi1 mutant mice display behavioral defects that are consistent with inner ear anomalies, as they are ataxic, circle, display head tilting behavior and do not respond to noise. They have a unique inner ear phenotype in that the vestibular and cochlear hair cells are differentially affected. Although Gfi1-deficient mice initially specify inner ear hair cells, these hair cells are disorganized in both the vestibule and cochlea. The outer hair cells of the cochlea are improperly innervated and express neuronal markers that are not normally expressed in these cells. Furthermore, Gfi1 mutant mice lose all cochlear hair cells just prior to and soon after birth through apoptosis. Finally, by five months of age there is also a dramatic reduction in the number of cochlear neurons. Hence, Gfi1 is expressed in the developing nervous system, is required for inner ear hair cell differentiation, and its loss

  6. Ongoing cell death and immune influences on regeneration in the vestibular sensory organs

    NASA Technical Reports Server (NTRS)

    Warchol, M. E.; Matsui, J. I.; Simkus, E. L.; Ogilive, J. M.

    2001-01-01

    Hair cells in the vestibular organs of birds have a relatively short life span. Mature hair cells appear to die spontaneously and are then quickly replaced by new hair cells that arise from the division of epithelial supporting cells. A similar regenerative mechanism also results in hair cell replacement after ototoxic damage. The cellular basis of hair cell turnover in the avian ear is not understood. We are investigating the signaling pathways that lead to hair cell death and the relationship between ongoing cell death and cell production. In addition, work from our lab and others has demonstrated that the avian inner ear contains a resident population of macrophages and that enhanced numbers of macrophages are recruited to sites of hair cells lesions. Those observations suggest that macrophages and their secretory products (cytokines) may be involved in hair cell regeneration. Consistent with that suggestion, we have found that treatment with the anti-inflammatory drug dexamethasone reduces regenerative cell proliferation in the avian ear, and that certain macrophage-secreted cytokines can influence the proliferation of vestibular supporting cells and the survival of statoacoustic neurons. Those results suggest a role for the immune system in the process of sensory regeneration in the inner ear.

  7. A short history of nearly every sense - The evolutionary history of vertebrate sensory cell types.

    PubMed

    Schlosser, Gerhard

    2018-05-08

    Evolving from filter feeding chordate ancestors, vertebrates adopted a more active life style. These ecological and behavioral changes went along with an elaboration of the vertebrate head including novel complex paired sense organs such as the eyes, inner ears and olfactory epithelia. However, the photoreceptors, mechanoreceptors and chemoreceptors used in these sense organs have a long evolutionary history and homologous cell types can be recognized in many other bilaterians or even cnidarians. After briefly introducing some of the major sensory cell types found in vertebrates, this review summarizes the phylogenetic distribution of sensory cell types in metazoans and presents a scenario for the evolutionary history of various sensory cell types involving several cell type diversification and fusion events. It is proposed that the evolution of novel cranial sense organs in vertebrates involved the redeployment of evolutionarily ancient sensory cell types for building larger and more complex sense organs.

  8. Wild-type cells rescue genotypically Math1-null hair cells in the inner ears of chimeric mice.

    PubMed

    Du, Xiaoping; Jensen, Patricia; Goldowitz, Daniel; Hamre, Kristin M

    2007-05-15

    The transcription factor Math1 has been shown to be critical in the formation of hair cells (HCs) in the inner ear. However, the influence of environmental factors in HC specification suggests that cell extrinsic factors are also crucial to their development. To test whether extrinsic factors impact development of Math1-null (Math1(beta-Gal/beta-Gal)) HCs, we examined neonatal (postnatal ages P0-P4.5) Math1-null chimeric mice in which genotypically mutant and wild-type cells intermingle to form the inner ear. We provide the first direct evidence that Math1-null HCs are able to be generated and survive in the conducive chimeric environment. beta-Galactosidase expression was used to identify genetically mutant cells while cells were phenotypically defined as HCs by morphological characteristics notably the expression of HC-specific markers. Genotypically mutant HCs were found in all sensory epithelia of the inner ear at all ages examined. Comparable results were obtained irrespective of the wild-type component of the chimeric mice. Thus, genotypically mutant cells retain the competence to differentiate into HCs. The implication is that the lack of the Math1 gene in HC precursors can be overcome by environmental influences, such as cell-cell interactions with wild-type cells, to ultimately result in the formation of HCs.

  9. Vitamin D receptor deficiency impairs inner ear development in zebrafish

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kwon, Hye-Joo; Biology Department, Princess Nourah University, Riyadh 11671

    The biological actions of vitamin D are largely mediated through binding to the vitamin D receptor (VDR), a member of the nuclear hormone receptor family, which regulates gene expression in a wide variety of tissues and cells. Mutations in VDR gene have been implicated in ear disorders (hearing loss and balance disorder) but the mechanisms are not well established. In this study, to investigate the role of VDR in inner ear development, morpholino-mediated gene knockdown approaches were used in zebrafish model system. Two paralogs for VDR, vdra and vdrb, have been identified in zebrafish. Knockdown of vdra had no effectmore » on ear development, whereas knockdown of vdrb displayed morphological ear defects including smaller otic vesicles with malformed semicircular canals and abnormal otoliths. Loss-of-vdrb resulted in down-regulation of pre-otic markers, pax8 and pax2a, indicating impairment of otic induction. Furthermore, zebrafish embryos lacking vdrb produced fewer sensory hair cells in the ears and showed disruption of balance and motor coordination. These data reveal that VDR signaling plays an important role in ear development. - Highlights: • VDR signaling is involved in ear development. • Knockdown of vdrb causes inner ear malformations during embryogenesis. • Knockdown of vdrb affects otic placode induction. • Knockdown of vdrb reduces the number of sensory hair cells in the inner ear. • Knockdown of vdrb disrupts balance and motor coordination.« less

  10. Changes in the Adult Vertebrate Auditory Sensory Epithelium After Trauma

    PubMed Central

    Oesterle, Elizabeth C.

    2012-01-01

    Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells. In contrast, injured non-mammalian vertebrate ear generates replacement hair cells to restore hearing functions. Non-sensory support cells within the auditory epithelium play key roles in the repair processes. PMID:23178236

  11. Cytoskeletal changes in actin and microtubules underlie the developing surface mechanical properties of sensory and supporting cells in the mouse cochlea

    PubMed Central

    Szarama, Katherine B.; Gavara, Núria; Petralia, Ronald S.; Kelley, Matthew W.; Chadwick, Richard S.

    2012-01-01

    Correct patterning of the inner ear sensory epithelium is essential for the conversion of sound waves into auditory stimuli. Although much is known about the impact of the developing cytoskeleton on cellular growth and cell shape, considerably less is known about the role of cytoskeletal structures on cell surface mechanical properties. In this study, atomic force microscopy (AFM) was combined with fluorescence imaging to show that developing inner ear hair cells and supporting cells have different cell surface mechanical properties with different developmental time courses. We also explored the cytoskeletal organization of developing sensory and non-sensory cells, and used pharmacological modulation of cytoskeletal elements to show that the developmental increase of hair cell stiffness is a direct result of actin filaments, whereas the development of supporting cell surface mechanical properties depends on the extent of microtubule acetylation. Finally, this study found that the fibroblast growth factor signaling pathway is necessary for the developmental time course of cell surface mechanical properties, in part owing to the effects on microtubule structure. PMID:22573615

  12. Ick Ciliary Kinase Is Essential for Planar Cell Polarity Formation in Inner Ear Hair Cells and Hearing Function.

    PubMed

    Okamoto, Shio; Chaya, Taro; Omori, Yoshihiro; Kuwahara, Ryusuke; Kubo, Shun; Sakaguchi, Hirofumi; Furukawa, Takahisa

    2017-02-22

    Cellular asymmetries play crucial roles in development and organ function. The planar cell polarity (PCP) signaling pathway is involved in the establishment of cellular asymmetry within the plane of a cell sheet. Inner ear sensory hair cells (HCs), which have several rows of staircase-like stereocilia and one kinocilium located at the vertex of the stereocilia protruding from the apical surface of each HC, exhibit a typical form of PCP. Although connections between cilia and PCP signaling in vertebrate development have been reported, their precise nature is not well understood. During inner ear development, several ciliary proteins are known to play a role in PCP formation. In the current study, we investigated a functional role for intestinal cell kinase (Ick), which regulates intraflagellar transport (IFT) at the tip of cilia, in the mouse inner ear. A lack of Ick in the developing inner ear resulted in PCP defects in the cochlea, including misorientation or misshaping of stereocilia and aberrant localization of the kinocilium and basal body in the apical and middle turns, leading to auditory dysfunction. We also observed abnormal ciliary localization of Ift88 in both HCs and supporting cells. Together, our results show that Ick ciliary kinase is essential for PCP formation in inner ear HCs, suggesting that ciliary transport regulation is important for PCP signaling. SIGNIFICANCE STATEMENT The cochlea in the inner ear is the hearing organ. Planar cell polarity (PCP) in hair cells (HCs) in the cochlea is essential for mechanotransduction and refers to the asymmetric structure consisting of stereociliary bundles and the kinocilium on the apical surface of the cell body. We reported previously that a ciliary kinase, Ick, regulates intraflagellar transport (IFT). Here, we found that loss of Ick leads to abnormal localization of the IFT component in kinocilia, PCP defects in HCs, and hearing dysfunction. Our study defines the association of ciliary transport

  13. Sox2 and Jagged1 Expression in Normal and Drug-Damaged Adult Mouse Inner Ear

    PubMed Central

    Campbell, Sean; Taylor, Ruth R.; Forge, Andrew; Hume, Clifford R.

    2007-01-01

    Inner ear hair cells detect environmental signals associated with hearing, balance, and body orientation. In humans and other mammals, significant hair cell loss leads to irreversible hearing and balance deficits, whereas hair cell loss in nonmammalian vertebrates is repaired by the spontaneous generation of replacement hair cells. Research in mammalian hair cell regeneration is hampered by the lack of in vivo damage models for the adult mouse inner ear and the paucity of cell-type-specific markers for non-sensory cells within the sensory receptor epithelia. The present study delineates a protocol to drug damage the adult mouse auditory epithelium (organ of Corti) in situ and uses this protocol to investigate Sox2 and Jagged1 expression in damaged inner ear sensory epithelia. In other tissues, the transcription factor Sox2 and a ligand member of the Notch signaling pathway, Jagged1, are involved in regenerative processes. Both are involved in early inner ear development and are expressed in developing support cells, but little is known about their expressions in the adult. We describe a nonsurgical technique for inducing hair cell damage in adult mouse organ of Corti by a single high-dose injection of the aminoglycoside kanamycin followed by a single injection of the loop diuretic furosemide. This drug combination causes the rapid death of outer hair cells throughout the cochlea. Using immunocytochemical techniques, Sox2 is shown to be expressed specifically in support cells in normal adult mouse inner ear and is not affected by drug damage. Sox2 is absent from auditory hair cells, but is expressed in a subset of vestibular hair cells. Double-labeling experiments with Sox2 and calbindin suggest Sox2-positive hair cells are Type II. Jagged1 is also expressed in support cells in the adult ear and is not affected by drug damage. Sox2 and Jagged1 may be involved in the maintenance of support cells in adult mouse inner ear. PMID:18157569

  14. Dimethyl sulfoxide (DMSO) exacerbates cisplatin-induced sensory hair cell death in zebrafish (Danio rerio).

    PubMed

    Uribe, Phillip M; Mueller, Melissa A; Gleichman, Julia S; Kramer, Matthew D; Wang, Qi; Sibrian-Vazquez, Martha; Strongin, Robert M; Steyger, Peter S; Cotanche, Douglas A; Matsui, Jonathan I

    2013-01-01

    Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO.

  15. Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)

    PubMed Central

    Gleichman, Julia S.; Kramer, Matthew D.; Wang, Qi; Sibrian-Vazquez, Martha; Strongin, Robert M.; Steyger, Peter S.; Cotanche, Douglas A.; Matsui, Jonathan I.

    2013-01-01

    Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO. PMID:23383324

  16. Three-dimensional Organotypic Cultures of Vestibular and Auditory Sensory Organs.

    PubMed

    Gnedeva, Ksenia; Hudspeth, A J; Segil, Neil

    2018-06-01

    The sensory organs of the inner ear are challenging to study in mammals due to their inaccessibility to experimental manipulation and optical observation. Moreover, although existing culture techniques allow biochemical perturbations, these methods do not provide a means to study the effects of mechanical force and tissue stiffness during development of the inner ear sensory organs. Here we describe a method for three-dimensional organotypic culture of the intact murine utricle and cochlea that overcomes these limitations. The technique for adjustment of a three-dimensional matrix stiffness described here permits manipulation of the elastic force opposing tissue growth. This method can therefore be used to study the role of mechanical forces during inner ear development. Additionally, the cultures permit virus-mediated gene delivery, which can be used for gain- and loss-of-function experiments. This culture method preserves innate hair cells and supporting cells and serves as a potentially superior alternative to the traditional two-dimensional culture of vestibular and auditory sensory organs.

  17. Responses of the ear to low frequency sounds, infrasound and wind turbines.

    PubMed

    Salt, Alec N; Hullar, Timothy E

    2010-09-01

    Infrasonic sounds are generated internally in the body (by respiration, heartbeat, coughing, etc) and by external sources, such as air conditioning systems, inside vehicles, some industrial processes and, now becoming increasingly prevalent, wind turbines. It is widely assumed that infrasound presented at an amplitude below what is audible has no influence on the ear. In this review, we consider possible ways that low frequency sounds, at levels that may or may not be heard, could influence the function of the ear. The inner ear has elaborate mechanisms to attenuate low frequency sound components before they are transmitted to the brain. The auditory portion of the ear, the cochlea, has two types of sensory cells, inner hair cells (IHC) and outer hair cells (OHC), of which the IHC are coupled to the afferent fibers that transmit "hearing" to the brain. The sensory stereocilia ("hairs") on the IHC are "fluid coupled" to mechanical stimuli, so their responses depend on stimulus velocity and their sensitivity decreases as sound frequency is lowered. In contrast, the OHC are directly coupled to mechanical stimuli, so their input remains greater than for IHC at low frequencies. At very low frequencies the OHC are stimulated by sounds at levels below those that are heard. Although the hair cells in other sensory structures such as the saccule may be tuned to infrasonic frequencies, auditory stimulus coupling to these structures is inefficient so that they are unlikely to be influenced by airborne infrasound. Structures that are involved in endolymph volume regulation are also known to be influenced by infrasound, but their sensitivity is also thought to be low. There are, however, abnormal states in which the ear becomes hypersensitive to infrasound. In most cases, the inner ear's responses to infrasound can be considered normal, but they could be associated with unfamiliar sensations or subtle changes in physiology. This raises the possibility that exposure to the

  18. Engraftment of Human Pluripotent Stem Cell-derived Progenitors in the Inner Ear of Prenatal Mice.

    PubMed

    Takeda, Hiroki; Hosoya, Makoto; Fujioka, Masato; Saegusa, Chika; Saeki, Tsubasa; Miwa, Toru; Okano, Hideyuki; Minoda, Ryosei

    2018-01-31

    There is, at present, no curative treatment for genetic hearing loss. We have previously reported that transuterine gene transfer of wild type CONNEXIN30 (CX30) genes into otocysts in CX30-deleted mice could restore hearing. Cell transplantation therapy might be another therapeutic option, although it is still unknown whether stem cell-derived progenitor cells could migrate into mouse otocysts. Here, we show successful cell transplantation of progenitors of outer sulcus cell-like cells derived from human-derived induced pluripotent stem cells into mouse otocysts on embryonic day 11.5. The delivered cells engrafted more frequently in the non-sensory region in the inner ear of CX30-deleted mice than in wild type mice and survived for up to 1 week after transplantation. Some of the engrafted cells expressed CX30 proteins in the non-sensory region. This is the first report that demonstrates successful engraftment of exogenous cells in prenatal developing otocysts in mice. Future studies using this mouse otocystic injection model in vivo will provide further clues for developing treatment modalities for congenital hearing loss in humans.

  19. Whole-mount Confocal Microscopy for Adult Ear Skin: A Model System to Study Neuro-vascular Branching Morphogenesis and Immune Cell Distribution.

    PubMed

    Yamazaki, Tomoko; Li, Wenling; Mukouyama, Yoh-Suke

    2018-03-29

    Here, we present a protocol of a whole-mount adult ear skin imaging technique to study comprehensive three-dimensional neuro-vascular branching morphogenesis and patterning, as well as immune cell distribution at a cellular level. The analysis of peripheral nerve and blood vessel anatomical structures in adult tissues provides some insights into the understanding of functional neuro-vascular wiring and neuro-vascular degeneration in pathological conditions such as wound healing. As a highly informative model system, we have focused our studies on adult ear skin, which is readily accessible for dissection. Our simple and reproducible protocol provides an accurate depiction of the cellular components in the entire skin, such as peripheral nerves (sensory axons, sympathetic axons, and Schwann cells), blood vessels (endothelial cells and vascular smooth muscle cells), and inflammatory cells. We believe this protocol will pave the way to investigate morphological abnormalities in peripheral nerves and blood vessels as well as the inflammation in the adult ear skin under different pathological conditions.

  20. Responses of the ear to low frequency sounds, infrasound and wind turbines

    PubMed Central

    Salt, Alec N.; Hullar, Timothy E.

    2010-01-01

    Infrasonic sounds are generated internally in the body (by respiration, heartbeat, coughing, etc) and by external sources, such as air conditioning systems, inside vehicles, some industrial processes and, now becoming increasingly prevalent, wind turbines. It is widely assumed that infrasound presented at an amplitude below what is audible has no influence on the ear. In this review, we consider possible ways that low frequency sounds, at levels that may or may not be heard, could influence the function of the ear. The inner ear has elaborate mechanisms to attenuate low frequency sound components before they are transmitted to the brain. The auditory portion of the ear, the cochlea, has two types of sensory cells, inner hair cells (IHC) and outer hair cells (OHC), of which the IHC are coupled to the afferent fibers that transmit “hearing” to the brain. The sensory stereocilia (“hairs”) on the IHC are “fluid coupled” to mechanical stimuli, so their responses depend on stimulus velocity and their sensitivity decreases as sound frequency is lowered. In contrast, the OHC are directly coupled to mechanical stimuli, so their input remains greater than for IHC at low frequencies. At very low frequencies the OHC are stimulated by sounds at levels below those that are heard. Although the hair cells in other sensory structures such as the saccule may be tuned to infrasonic frequencies, auditory stimulus coupling to these structures is inefficient so that they are unlikely to be influenced by airborne infrasound. Structures that are involved in endolymph volume regulation are also known to be influenced by infrasound, but their sensitivity is also thought to be low. There are, however, abnormal states in which the ear becomes hypersensitive to infrasound. In most cases, the inner ear’s responses to infrasound can be considered normal, but they could be associated with unfamiliar sensations or subtle changes in physiology. This raises the possibility that

  1. Daple coordinates organ-wide and cell-intrinsic polarity to pattern inner-ear hair bundles

    PubMed Central

    Siletti, Kimberly; Hudspeth, A. J.

    2017-01-01

    The establishment of planar polarization by mammalian cells necessitates the integration of diverse signaling pathways. In the inner ear, at least two systems regulate the planar polarity of sensory hair bundles. The core planar cell polarity (PCP) proteins coordinate the orientations of hair cells across the epithelial plane. The cell-intrinsic patterning of hair bundles is implemented independently by the G protein complex classically known for orienting the mitotic spindle. Although the primary cilium also participates in each of these pathways, its role and the integration of the two systems are poorly understood. We show that Dishevelled-associating protein with a high frequency of leucine residues (Daple) interacts with PCP and cell-intrinsic signals. Regulated by the cell-intrinsic pathway, Daple is required to maintain the polarized distribution of the core PCP protein Dishevelled and to position the primary cilium at the abneural edge of the apical surface. Our results suggest that the primary cilium or an associated structure influences the domain of cell-intrinsic signals that shape the hair bundle. Daple is therefore essential to orient and pattern sensory hair bundles. PMID:29229865

  2. Localization of soluble guanylate cyclase activity in the guinea pig inner ear.

    PubMed

    Takumida, M; Anniko, M; Popa, R; Zhang, D M

    2000-01-01

    The aim of this study was to characterize the nitric oxide (NO) receptor soluble guanylate cyclase (sGC), to determine the cells targeted by NO and to elucidate the function of the NO/cGMP pathway in the inner ear. sGC activity in the inner ear was localized by immunohistochemical detection of NO-stimulated cGMP. Soluble guanylate cyclase activity in the cochlea was detected in the nerve endings underneath the outer and inner hair cells, supporting cells, stria vascularis and vessels. In the vestibular organs, sGC activity was detected in the cytoplasm of sensory cells, nerve fibres, dark cells and transitional cells and vessels. These findings suggest that the NO/cGMP pathway may be involved in regulatory processes in neurotransmission, blood flow and inner ear fluid homeostasis.

  3. Evolution and development of the vertebrate ear

    NASA Technical Reports Server (NTRS)

    Fritzsch, B.; Beisel, K. W.

    2001-01-01

    This review outlines major aspects of development and evolution of the ear, specifically addressing issues of cell fate commitment and the emerging molecular governance of these decisions. Available data support the notion of homology of subsets of mechanosensors across phyla (proprioreceptive mechanosensory neurons in insects, hair cells in vertebrates). It is argued that this conservation is primarily related to the specific transducing environment needed to achieve mechanosensation. Achieving this requires highly conserved transcription factors that regulate the expression of the relevant structural genes for mechanosensory transduction. While conserved at the level of some cell fate assignment genes (atonal and its mammalian homologue), the ear has also radically reorganized its development by implementing genes used for cell fate assignment in other parts of the developing nervous systems (e.g., neurogenin 1) and by evolving novel sets of genes specifically associated with the novel formation of sensory neurons that contact hair cells (neurotrophins and their receptors). Numerous genes have been identified that regulate morphogenesis, but there is only one common feature that emerges at the moment: the ear appears to have co-opted genes from a large variety of other parts of the developing body (forebrain, limbs, kidneys) and establishes, in combination with existing transcription factors, an environment in which those genes govern novel, ear-related morphogenetic aspects. The ear thus represents a unique mix of highly conserved developmental elements combined with co-opted and newly evolved developmental elements.

  4. Expression and function of FGF10 in mammalian inner ear development

    NASA Technical Reports Server (NTRS)

    Pauley, Sarah; Wright, Tracy J.; Pirvola, Ulla; Ornitz, David; Beisel, Kirk; Fritzsch, Bernd

    2003-01-01

    We have investigated the expression of FGF10 during ear development and the effect of an FGF10 null mutation on ear development. Our in situ hybridization data reveal expression of FGF10 in all three canal crista sensory epithelia and the cochlea anlage as well as all sensory neurons at embryonic day 11.5 (E11.5). Older embryos (E18.5) displayed strong graded expression in all sensory epithelia. FGF10 null mutants show complete agenesis of the posterior canal crista and the posterior canal. The posterior canal sensory neurons form initially and project rather normally by E11.5, but they disappear within 2 days. FGF10 null mutants have no posterior canal system at E18.5. In addition, these mutants have deformations of the anterior and horizontal cristae, reduced formation of the anterior and horizontal canals, as well as altered position of the remaining sensory epithelia with respect to the utricle. Hair cells form but some have defects in their cilia formation. No defects were detected in the organ of Corti at the cellular level. Together these data suggest that FGF10 plays a major role in ear morphogenesis. Most of these data are consistent with earlier findings on a null mutation in FGFR2b, one of FGF10's main receptors. Copyright 2003 Wiley-Liss, Inc.

  5. Inner ear progenitor cells can be generated in vitro from human bone marrow mesenchymal stem cells.

    PubMed

    Boddy, Sarah L; Chen, Wei; Romero-Guevara, Ricardo; Kottam, Lucksy; Bellantuono, Illaria; Rivolta, Marcelo N

    2012-11-01

    Mouse mesenchymal stem cells (MSCs) can generate sensory neurons and produce inner ear hair cell-like cells. An equivalent source from humans is highly desirable, given their potential application in patient-specific regenerative therapies for deafness. In this study, we explored the ability of human MSCs (hMSCs) to differentiate into otic lineages. hMSCs were exposed to culture media conditioned by human fetal auditory stem cells. Conditioned media induced the expression of otic progenitor markers PAX8, PAX2, GATA3 and SOX2. After 4 weeks, cells coexpressed ATOH1, MYO7A and POU4F3 (indicators of hair cell lineage) or neuronal markers NEUROG1, POU4F1 and NEFH. Inhibition of WNT signaling prevented differentiation into otic progenitors, while WNT activation partially phenocopied results seen with the conditioned media. This study demonstrates that hMSCs can be driven to express key genes found in the otic lineages and thereby promotes their status as candidates for regenerative therapies for deafness.

  6. Hair cell regeneration

    PubMed Central

    Edge, Albert SB; Chen, Zheng-Yi

    2017-01-01

    The mammalian inner ear largely lacks the capacity to regenerate hair cells, the sensory cells required for hearing and balance. Recent studies in both lower vertebrates and mammals have uncovered genes and pathways important in hair cell development and have suggested ways that the sensory epithelia could be manipulated to achieve hair cell regeneration. These approaches include the use of inner ear stem cells, transdifferentiation of nonsensory cells, and induction of a proliferative response in the cells that can become hair cells. PMID:18929656

  7. Defective calmodulin-dependent rapid apical endocytosis in zebrafish sensory hair cell mutants.

    PubMed

    Seiler, C; Nicolson, T

    1999-11-15

    Vertebrate mechanosensory hair cells contain a narrow "pericuticular" zone which is densely populated with small vesicles between the cuticular plate and cellular junctions near the apical surface. The presence of many cytoplasmic vesicles suggests that the apical surface of hair cells has a high turnover rate. The significance of intense membrane trafficking at the apical surface is not known. Using a marker of endocytosis, the styryl dye FM1-43, this report shows that rapid apical endocytosis in zebrafish lateral line sensory hair cells is calcium and calmodulin dependent and is partially blocked by the presence of amiloride and dihydrostreptomycin, known inhibitors of mechanotransduction channels. As seen in lateral line hair cells, sensory hair cells within the larval otic capsule also exhibit rapid apical endocytosis. Defects in internalization of the dye in both lateral line and inner ear hair cells were found in five zebrafish auditory/vestibular mutants: sputnik, mariner, orbiter, mercury, and skylab. In addition, lateral line hair cells in these mutants were not sensitive to prolonged exposure to streptomycin, which is toxic to hair cells. The presence of endocytic defects in the majority of zebrafish mechanosensory mutants points to a important role of apical endocytosis in hair cell function. Copyright 1999 John Wiley & Sons, Inc.

  8. Inner Ear Morphology in the Atlantic Molly Poecilia mexicana—First Detailed Microanatomical Study of the Inner Ear of a Cyprinodontiform Species

    PubMed Central

    Schulz-Mirbach, Tanja; Heß, Martin; Plath, Martin

    2011-01-01

    Background Fishes show an amazing diversity in hearing abilities, inner ear structures, and otolith morphology. Inner ear morphology, however, has not yet been investigated in detail in any member of the diverse order Cyprinodontiformes. We, therefore, studied the inner ear of the cyprinodontiform freshwater fish Poecilia mexicana by analyzing the position of otoliths in situ, investigating the 3D structure of sensory epithelia, and examining the orientation patterns of ciliary bundles of the sensory hair cells, while combining μ-CT analyses, scanning electron microscopy, and immunocytochemical methods. P. mexicana occurs in different ecotypes, enabling us to study the intra-specific variability (on a qualitative basis) of fish from regular surface streams, and the Cueva del Azufre, a sulfidic cave in southern Mexico. Results The inner ear of Poecilia mexicana displays a combination of several remarkable features. The utricle is connected rostrally instead of dorso-rostrally to the saccule, and the macula sacculi, therefore, is very close to the utricle. Moreover, the macula sacculi possesses dorsal and ventral bulges. The two studied ecotypes of P. mexicana showed variation mainly in the shape and curvature of the macula lagenae, in the curvature of the macula sacculi, and in the thickness of the otolithic membrane. Conclusions Our study for the first time provides detailed insights into the auditory periphery of a cyprinodontiform inner ear and thus serves a basis—especially with regard to the application of 3D techniques—for further research on structure-function relationships of inner ears within the species-rich order Cyprinodontiformes. We suggest that other poeciliid taxa, or even other non-poeciliid cyprinodontiforms, may display similar inner ear morphologies as described here. PMID:22110746

  9. Inner ear morphology in the Atlantic molly Poecilia mexicana--first detailed microanatomical study of the inner ear of a cyprinodontiform species.

    PubMed

    Schulz-Mirbach, Tanja; Hess, Martin; Plath, Martin

    2011-01-01

    Fishes show an amazing diversity in hearing abilities, inner ear structures, and otolith morphology. Inner ear morphology, however, has not yet been investigated in detail in any member of the diverse order Cyprinodontiformes. We, therefore, studied the inner ear of the cyprinodontiform freshwater fish Poecilia mexicana by analyzing the position of otoliths in situ, investigating the 3D structure of sensory epithelia, and examining the orientation patterns of ciliary bundles of the sensory hair cells, while combining μ-CT analyses, scanning electron microscopy, and immunocytochemical methods. P. mexicana occurs in different ecotypes, enabling us to study the intra-specific variability (on a qualitative basis) of fish from regular surface streams, and the Cueva del Azufre, a sulfidic cave in southern Mexico. The inner ear of Poecilia mexicana displays a combination of several remarkable features. The utricle is connected rostrally instead of dorso-rostrally to the saccule, and the macula sacculi, therefore, is very close to the utricle. Moreover, the macula sacculi possesses dorsal and ventral bulges. The two studied ecotypes of P. mexicana showed variation mainly in the shape and curvature of the macula lagenae, in the curvature of the macula sacculi, and in the thickness of the otolithic membrane. Our study for the first time provides detailed insights into the auditory periphery of a cyprinodontiform inner ear and thus serves a basis--especially with regard to the application of 3D techniques--for further research on structure-function relationships of inner ears within the species-rich order Cyprinodontiformes. We suggest that other poeciliid taxa, or even other non-poeciliid cyprinodontiforms, may display similar inner ear morphologies as described here.

  10. Hair cell regeneration in sensory epithelia from the inner ear of a urodele amphibian.

    PubMed

    Taylor, Ruth R; Forge, Andrew

    2005-03-28

    The capacity of urodele amphibians to regenerate a variety of body parts is providing insight into mechanisms of tissue regeneration in vertebrates. In this study the ability of the newt, Notophthalmus viridescens, to regenerate inner ear hair cells in vitro was examined. Intact otic capsules were maintained in organotypic culture. Incubation in 2 mM gentamicin for 48 hours resulted in ablation of all hair cells from the saccular maculae. Thus, any hair cell recovery was not due to repair of damaged hair cells. Immature hair cells were subsequently observed at approximately 12 days posttreatment. Their number increased over the following 7-14 days to reach approximately 30% of the normal number. Following incubation of damaged tissue with bromodeoxyuridine (BrdU), labeled nuclei were confined strictly within regions of hair cell loss, indicating that supporting cells entered S-phase. Double labeling of tissue with two different hair cell markers and three different antibodies to BrdU in various combinations, however, all showed that the nuclei of cells that labeled with hair cell markers did not label for BrdU. This suggested that the new hair cells were not derived from those cells that had undergone mitosis. When mitosis was blocked with aphidicolin, new hair cells were still generated. The results suggest that direct phenotypic conversion of supporting cells into hair cells without an intervening mitotic event is a major mechanism of hair cell regeneration in the newt. A similar mechanism has been proposed for the hair cell recovery phenomenon observed in the vestibular organs of mammals. Copyright 2005 Wiley-Liss, Inc.

  11. Vitamin D receptor deficiency impairs inner ear development in zebrafish.

    PubMed

    Kwon, Hye-Joo

    2016-09-16

    The biological actions of vitamin D are largely mediated through binding to the vitamin D receptor (VDR), a member of the nuclear hormone receptor family, which regulates gene expression in a wide variety of tissues and cells. Mutations in VDR gene have been implicated in ear disorders (hearing loss and balance disorder) but the mechanisms are not well established. In this study, to investigate the role of VDR in inner ear development, morpholino-mediated gene knockdown approaches were used in zebrafish model system. Two paralogs for VDR, vdra and vdrb, have been identified in zebrafish. Knockdown of vdra had no effect on ear development, whereas knockdown of vdrb displayed morphological ear defects including smaller otic vesicles with malformed semicircular canals and abnormal otoliths. Loss-of-vdrb resulted in down-regulation of pre-otic markers, pax8 and pax2a, indicating impairment of otic induction. Furthermore, zebrafish embryos lacking vdrb produced fewer sensory hair cells in the ears and showed disruption of balance and motor coordination. These data reveal that VDR signaling plays an important role in ear development. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Regeneration and replacement in the vertebrate inner ear.

    PubMed

    Matsui, Jonathan I; Parker, Mark A; Ryals, Brenda M; Cotanche, Douglas A

    2005-10-01

    Deafness affects more than 40 million people in the UK and the USA, and many more world-wide. The primary cause of hearing loss is damage to or death of the sensory receptor cells in the inner ear, the hair cells. Birds can readily regenerate their cochlear hair cells but the mammalian cochlea has shown no ability to regenerate after damage. Current research efforts are focusing on gene manipulation, gene therapy and stem cell transplantation for repairing or replacing damaged mammalian cochlear hair cells, which could lead to therapies for treating deafness in humans.

  13. Activation of apoptotic pathways in the absence of cell death in an inner-ear immortomouse cell line

    PubMed Central

    Chen, Fu-Quan; Hill, Kayla; Guan, Ya-Jun; Schacht, Jochen; Sha, Su-Hua

    2012-01-01

    Aminoglycoside antibiotics and cisplatin (CDDP) are the major ototoxins of clinical medicine due to their capacity to cause significant, as well as permanent hearing loss by targeting the mammalian sensory cells. Understanding the pathogenesis of damage is the first step in designing effective prevention of drug-induced hearing loss. In-vitro systems greatly enhance the efficiency of biochemical and molecular investigations through ease of access and manipulation. HEI-OC1, an inner ear cell line derived from the immortomouse, expresses markers for auditory sensory cells and, therefore, is a potential tool to study the ototoxic mechanisms of drugs like aminoglycoside antibiotics and CDDP. HEI-OC1 cells (and also HeLa cells) efficiently take up fluorescently tagged gentamicin and respond to drug treatment with changes in cell death and survival signaling pathways. Within hours, the C-jun N-terminal kinase pathway and the transcription factor AP-1 were activated and at later times, the “executioner caspase”, caspase-3. These responses were robust and elicited by both gentamicin and kanamycin. However, despite the initiation of apoptotic pathways and transient changes in nuclear morphology, cell death was not observed following aminoglycoside treatment, while administration of CDDP lead to significant cell death as determined by flow cytometric measurements; β-galactosidase analysis ruled out senescence in gentamicin-treated cells. The ability to withstand treatment with aminoglycosides but not with CDDP suggests that this cell line might be helpful in providing some insight into the differential actions of the two ototoxic drugs. PMID:22240458

  14. Investigating Science Student Teachers' Ideas about Function and Anatomical Form of Two Human Sensory Organs, the Eye and the Ear

    ERIC Educational Resources Information Center

    Kunt, Halil

    2016-01-01

    The purpose of this research was to determine science student teachers' level of knowledge about the anatomical structure of two sensory organs, the eye and the ear, in addition to vision and hearing processes. Conducted with 86 science student teachers, research utilized drawing methods and open-ended questions as data collection instruments. The…

  15. Stem/progenitor cells derived from the cochlear sensory epithelium give rise to spheres with distinct morphologies and features.

    PubMed

    Diensthuber, Marc; Oshima, Kazuo; Heller, Stefan

    2009-06-01

    Nonmammalian vertebrates regenerate lost sensory hair cells by means of asymmetric division of supporting cells. Inner ear or lateral line supporting cells in birds, amphibians, and fish consequently serve as bona fide stem cells resulting in high regenerative capacity of hair cell-bearing organs. Hair cell regeneration does not happen in the mammalian cochlea, but cells with proliferative capacity can be isolated from the neonatal cochlea. These cells have the ability to form clonal floating colonies, so-called spheres, when cultured in nonadherent conditions. We noticed that the sphere population derived from mouse cochlear sensory epithelium cells was heterogeneous, consisting of morphologically distinct sphere types, hereby classified as solid, transitional, and hollow. Cochlear sensory epithelium-derived stem/progenitor cells initially give rise to small solid spheres, which subsequently transition into hollow spheres, a change that is accompanied by epithelial differentiation of the majority of sphere cells. Only solid spheres, and to a lesser extent, transitional spheres, appeared to harbor self-renewing stem cells, whereas hollow spheres could not be consistently propagated. Solid spheres contained significantly more rapidly cycling Pax-2-expressing presumptive otic progenitor cells than hollow spheres. Islet-1, which becomes upregulated in nascent sensory patches, was also more abundant in solid than in hollow spheres. Likewise, hair cell-like cells, characterized by the expression of multiple hair cell markers, differentiated in significantly higher numbers in cell populations derived from solid spheres. We conclude that cochlear sensory epithelium cell populations initially give rise to small solid spheres that have self-renewing capacity before they subsequently convert into hollow spheres, a process that is accompanied by loss of stemness and reduced ability to spontaneously give rise to hair cell-like cells. Solid spheres might, therefore, represent

  16. Molecular evolution of the vertebrate mechanosensory cell and ear.

    PubMed

    Fritzsch, Bernd; Beisel, Kirk W; Pauley, Sarah; Soukup, Garrett

    2007-01-01

    The molecular basis of mechanosensation, mechanosensory cell development and mechanosensory organ development is reviewed with an emphasis on its evolution. In contrast to eye evolution and development, which apparently modified a genetic program through intercalation of genes between the master control genes on the top (Pax6, Eya1, Six1) of the hierarchy and the structural genes (rhodopsin) at the bottom, the as yet molecularly unknown mechanosensory channel precludes such a firm conclusion for mechanosensors. However, recent years have seen the identification of several structural genes which are involved in mechanosensory tethering and several transcription factors controlling mechanosensory cell and organ development; these warrant the interpretation of available data in very much the same fashion as for eye evolution: molecular homology combined with potential morphological parallelism. This assertion of molecular homology is strongly supported by recent findings of a highly conserved set of microRNAs that appear to be associated with mechanosensory cell development across phyla. The conservation of transcription factors and their regulators fits very well to the known or presumed mechanosensory specializations which can be mostly grouped as variations of a common cellular theme. Given the widespread distribution of the molecular ability to form mechanosensory cells, it comes as no surprise that structurally different mechanosensory organs evolved in different phyla, presenting a variation of a common theme specified by a conserved set of transcription factors in their cellular development. Within vertebrates and arthropods, some mechanosensory organs evolved into auditory organs, greatly increasing sensitivity to sound through modifications of accessory structures to direct sound to the specific sensory epithelia. However, while great attention has been paid to the evolution of these accessory structures in vertebrate fossils, comparatively less attention has

  17. Calcium Gradients in the Fish inner Ear sensory Epithelium and otolithic Membrane: an Energy filtering Transmission electron Microscopy (EFTEM) Study

    NASA Astrophysics Data System (ADS)

    Ibsch, M.; Anken, R.; Rahmann, H.

    Inner ear otolith formation in fish is supposed to be performed by the molecular release of proteinacious precursor material from the sensory epithelia, followed by an undirected and diffuse precipitation of calcium carbonate (which is mainly responsible for the functionally important weight of otoliths). Previous experiments have shown, however, that otolith formation in terms of provision both of the protein matrix and of calcium is regulated by a (likely neuronal) feedback mechanism. This regulating mechanism effects a symmetrical crystallisation of the corresponding otoliths in the inner ears of both sides of the head, which is necessary for a correct graviperception and for maintenance of postural control; thus, asymmetrical otoliths can induce kinetoses (e.g., space motion sickness) both in human and fish. On the background of an obviously directed incorporation of calcium into otoliths, the site of origin of the otoliths's inorganic components such as calcium still remains obscure. Therefore, ultrastructural and element analytical investigations were undertaken to screen the calcium distribution within the macular epithelial region using fish as model system. Electron spectroscopic imaging (ESI) and electron energy loss spectra (EELS) revealed discrete calcium-precipitations in the extracellular space of the otolithic membrane as well as within the lumina of the epithelial sensory cells. The calcium particles were accumulated at the macular tight junctions and seemed to be distributed in an ascending intracellular and a descending extracellular gradient towards the otolith. Further distinct calcium containing crystals covered the peripheral proteinacious layer of the otolith. The remaining endolymphatic space of the otocyst was lacking calcium precipitates. Overall, the present results indicate that the apical region of the macular epithelium is involved in the controlled release of calcium. This finding is in complete agreement with a study using calcium

  18. Bone Marrow Stem Cells and Ear Framework Reconstruction.

    PubMed

    Karimi, Hamid; Emami, Seyed-Abolhassan; Olad-Gubad, Mohammad-Kazem

    2016-11-01

    Repair of total human ear loss or congenital lack of ears is one of the challenging issues in plastic and reconstructive surgery. The aim of the present study was 3D reconstruction of the human ear with cadaveric ear cartilages seeded with human mesenchymal stem cells. We used cadaveric ear cartilages with preserved perichondrium. The samples were divided into 2 groups: group A (cartilage alone) and group B (cartilage seeded with a mixture of fibrin powder and mesenchymal stem cell [1,000,000 cells/cm] used and implanted in back of 10 athymic rats). After 12 weeks, the cartilages were removed and shape, size, weight, flexibility, and chondrocyte viability were evaluated. P value <0.05 was considered significant. In group A, size and weight of cartilages clearly reduced (P < 0.05) and then shape and flexibility (torsion of cartilages in clockwise and counterclockwise directions) were evaluated, which were found to be significantly reduced (P > 0.05). After staining with hematoxylin and eosin and performing microscopic examination, very few live chondrocytes were found in group A. In group B, size and weight of samples were not changed (P < 0.05); the shape and flexibility of samples were well maintained (P < 0.05) and on performing microscopic examination of cartilage samples, many live chondrocytes were found in cartilage (15-20 chondrocytes in each microscopic field). In samples with human stem cell, all variables (size, shape, weight, and flexibility) were significantly maintained and abundant live chondrocytes were found on performing microscopic examination. This method may be used for reconstruction of full defect of auricles in humans.

  19. Characterizing human vestibular sensory epithelia for experimental studies: new hair bundles on old tissue and implications for therapeutic interventions in ageing

    PubMed Central

    Taylor, Ruth R.; Jagger, Daniel J.; Saeed, Shakeel R.; Axon, Patrick; Donnelly, Neil; Tysome, James; Moffatt, David; Irving, Richard; Monksfield, Peter; Coulson, Chris; Freeman, Simon R.; Lloyd, Simon K.; Forge, Andrew

    2015-01-01

    Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice. PMID:25818177

  20. Desmoplastic small round cell tumor of the middle ear: A case report.

    PubMed

    Xu, Jing; Yao, Mengwei; Yang, Xinxin; Liu, Tao; Wang, Shaohua; Ma, Dengdian; Li, Xiaoyu

    2018-04-01

    Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive and malignant tumor. This report describes a case involving DSRCT of the middle ear which no case has been reported in the literature till date. A 59-year-old Chinese man with a 40-year history of repeated suppuration of his right ear and 1-year history of drooping of the angle of mouth. The CT of the middle ear and brain scan and enhanced MRI showed space occupying lesion in the right middle ear. Desmoplastic small round cell tumor of the middle ear. After relevant examinations, radical mastoidectomy and subtotal temporal bone resection were performed on the right ear under general anesthesia. The patient underwent postoperative adjuvant chemoradiation therapy. The patient was counterchecked regularly,there was norecurrence of DSRCT of the middle ear. Four years after surgery, the CT and MRI of the middle ear mastoid showed right middle ear soft tissue shadow,but postoperative pathological results showed proliferative fibrous and vascular tissues with chronic inflammatory cell infiltration and necrosis. DSRCT is a relatively aggressive, malignant mesenchymal tumor, with a very poor prognosis.The diagnosis of DSRCT relies on immunohistological data. Early diagnosis, radical surgery, chemotherapy, and radiotherapy are considered a reasonable way to prolong survival.

  1. Role of skeletal muscle in ear development.

    PubMed

    Rot, Irena; Baguma-Nibasheka, Mark; Costain, Willard J; Hong, Paul; Tafra, Robert; Mardesic-Brakus, Snjezana; Mrduljas-Djujic, Natasa; Saraga-Babic, Mirna; Kablar, Boris

    2017-10-01

    The current paper is a continuation of our work described in Rot and Kablar, 2010. Here, we show lists of 10 up- and 87 down-regulated genes obtained by a cDNA microarray analysis that compared developing Myf5-/-:Myod-/- (and Mrf4-/-) petrous part of the temporal bone, containing middle and inner ear, to the control, at embryonic day 18.5. Myf5-/-:Myod-/- fetuses entirely lack skeletal myoblasts and muscles. They are unable to move their head, which interferes with the perception of angular acceleration. Previously, we showed that the inner ear areas most affected in Myf5-/-:Myod-/- fetuses were the vestibular cristae ampullaris, sensitive to angular acceleration. Our finding that the type I hair cells were absent in the mutants' cristae was further used here to identify a profile of genes specific to the lacking cell type. Microarrays followed by a detailed consultation of web-accessible mouse databases allowed us to identify 6 candidate genes with a possible role in the development of the inner ear sensory organs: Actc1, Pgam2, Ldb3, Eno3, Hspb7 and Smpx. Additionally, we searched for human homologues of the candidate genes since a number of syndromes in humans have associated inner ear abnormalities. Mutations in one of our candidate genes, Smpx, have been reported as the cause of X-linked deafness in humans. Our current study suggests an epigenetic role that mechanical, and potentially other, stimuli originating from muscle, play in organogenesis, and offers an approach to finding novel genes responsible for altered inner ear phenotypes.

  2. Characterizing human vestibular sensory epithelia for experimental studies: new hair bundles on old tissue and implications for therapeutic interventions in ageing.

    PubMed

    Taylor, Ruth R; Jagger, Daniel J; Saeed, Shakeel R; Axon, Patrick; Donnelly, Neil; Tysome, James; Moffatt, David; Irving, Richard; Monksfield, Peter; Coulson, Chris; Freeman, Simon R; Lloyd, Simon K; Forge, Andrew

    2015-06-01

    Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Structural Diversity in the Inner Ear of Teleost Fishes: Implications for Connections to the Mauthner Cell

    NASA Technical Reports Server (NTRS)

    Popper, Arthur N.; Edds-Walton, Peggy L.

    1995-01-01

    A body of literature suggests that the Mauthner cell startle response can be elicited by stimulation of the ear. While we know that there are projections to the M-cell from the ear, the specific endorgan(s) of the ear projecting to the M-cell are not known. Moreover, there are many reasons to question whether there is one pattern of inner ear to M-cell connection or whether the endorgan(s) projection to the M-cell varies in species that have different hearing capabilities of hearing structures. In this paper, we briefly review the structure of fish ears, with an emphasis on structural regionalization within the ear. We also review the central projections of the ear, along with a discussion of the limited data on projections to the M-cell.

  4. Continuous hair cell turnover in the inner ear vestibular organs of a mammal, the Daubenton's bat (Myotis daubentonii).

    PubMed

    Kirkegaard, M; Jørgensen, J M

    2000-02-01

    In both humans and mice the number of hair cells in the inner ear sensory epithelia declines with age, indicating cell death (Park et al. 1987; Rosenhall 1973). However, recent reports demonstrate the ability of the vestibular sensory epithelia to regenerate after injury (Forge et al. 1993, 1998; Kuntz and Oesterle 1998; Li and Forge 1997; Rubel et al. 1995; Tanyeri et al. 1995). Still, a continuous hair cell turnover in the vestibular epithelia has not previously been demonstrated in mature mammals. Bats are the only flying mammals, and they are known to live to a higher age than animals of equal size. The maximum age of many species is 20 years, with average lifespans of 4-6 years (Schober and Grimmberger 1989). Further, the young are fully developed and able to fly at the age of 2 months, and thus the vestibular organs are thought to be differentiated at that age. Consequently, long-lived mammals such as bats might compensate for the loss of hair cells by producing new hair cells in their postembryonic life. Here we show that the utricular macula of adult Daubenton's bats (more than 6 months old) contains innervated immature hair cells as well as apoptotic hair cells, which strongly indicates a continuous turnover of hair cells, as previously demonstrated in birds.

  5. Continuous Hair Cell Turnover in the Inner Ear Vestibular Organs of a Mammal, the Daubenton's Bat (Myotis daubentonii)

    NASA Astrophysics Data System (ADS)

    Kirkegaard, M.; Jørgensen, J. M.

    In both humans and mice the number of hair cells in the inner ear sensory epithelia declines with age, indicating cell death (Park et al. 1987; Rosenhall 1973). However, recent reports demonstrate the ability of the vestibular sensory epithelia to regenerate after injury (Forge et al. 1993, 1998; Kuntz and Oesterle 1998; Li and Forge 1997; Rubel et al. 1995; Tanyeri et al. 1995). Still, a continuous hair cell turnover in the vestibular epithelia has not previously been demonstrated in mature mammals. Bats are the only flying mammals, and they are known to live to a higher age than animals of equal size. The maximum age of many species is 20years, with average lifespans of 4-6years (Schober and Grimmberger 1989). Further, the young are fully developed and able to fly at the age of 2months, and thus the vestibular organs are thought to be differentiated at that age. Consequently, long-lived mammals such as bats might compensate for the loss of hair cells by producing new hair cells in their postembryonic life. Here we show that the utricular macula of adult Daubenton's bats (more than 6months old) contains innervated immature hair cells as well as apoptotic hair cells, which strongly indicates a continuous turnover of hair cells, as previously demonstrated in birds.

  6. Ankrd6 is a mammalian functional homolog of Drosophila planar cell polarity gene diego and regulates coordinated cellular orientation in the mouse inner ear.

    PubMed

    Jones, Chonnettia; Qian, Dong; Kim, Sun Myoung; Li, Shuangding; Ren, Dongdong; Knapp, Lindsey; Sprinzak, David; Avraham, Karen B; Matsuzaki, Fumio; Chi, Fanglu; Chen, Ping

    2014-11-01

    The coordinated polarization of neighboring cells within the plane of the tissue, known as planar cell polarity (PCP), is a recurring theme in biology. It is required for numerous developmental processes for the form and function of many tissues and organs across species. The genetic pathway regulating PCP was first discovered in Drosophila, and an analogous but distinct pathway is emerging in vertebrates. It consists of membrane protein complexes known as core PCP proteins that are conserved across species. Here we report that the over-expression of the murine Ankrd6 (mAnkrd6) gene that shares homology with Drosophila core PCP gene diego causes a typical PCP phenotype in Drosophila, and mAnkrd6 can rescue the loss of function of diego in Drosophila. In mice, mAnkrd6 protein is asymmetrically localized in cells of the inner ear sensory organs, characteristic of components of conserved core PCP complexes. The loss of mAnkrd6 causes PCP defects in the inner ear sensory organs. Moreover, canonical Wnt signaling is significantly increased in mouse embryonic fibroblasts from mAnkrd6 knockout mice in comparison to wild type controls. Together, these results indicated that mAnkrd6 is a functional homolog of the Drosophila diego gene for mammalian PCP regulation and act to suppress canonical Wnt signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Cell proliferation and hair cell addition in the ear of the goldfish, Carassius auratus

    NASA Technical Reports Server (NTRS)

    Lanford, P. J.; Presson, J. C.; Popper, A. N.

    1996-01-01

    Cell proliferation and hair cell addition have not been studied in the ears of otophysan fish, a group of species who have specialized hearing capabilities. In this study we used the mitotic S-phase marker bromodeoxyuridine (BrdU) to identify proliferating cells in the ear of one otophysan species, Carassius auratus (the goldfish). Animals were sacrificed at 3 h or 5 days postinjection with BrdU and processed for immunocytochemistry. The results of the study show that cell proliferation occurs in all of the otic endorgans and results in the addition of new hair cells. BrdU-labeled cells were distributed throughout all epithelia, including the primary auditory endorgan (saccule), where hair cell phenotypes vary considerably along the rostrocaudal axis. This study lays the groundwork for our transmission electron microscopy study of proliferative cells in the goldfish ear (Presson et al., Hearing Research 100 (1996) 10-20) as well as future studies of hair cell development in this species. The ability to predict, based on epithelial location, the future phenotype of developing hair cells in the saccule of the goldfish make that endorgan a particularly powerful model system for the investigation of early hair cell differentiation.

  8. Creatine supports propagation and promotes neuronal differentiation of inner ear progenitor cells.

    PubMed

    Di Santo, Stefano; Mina, Amir; Ducray, Angélique; Widmer, Hans R; Senn, Pascal

    2014-05-07

    Long-term propagation of inner ear-derived progenitor/stem cells beyond the third generation and differentiation into inner ear cell types has been shown to be feasible, but challenging. We investigated whether the known neuroprotective guanidine compound creatine (Cr) promotes propagation of inner ear progenitor/stem cells as mitogen-expanded neurosphere cultures judged from the formation of spheres over passages. In addition, we studied whether Cr alone or in combination with brain-derived neurotrophic factor (BDNF) promotes neuronal differentiation of inner ear progenitors. For this purpose, early postnatal rat spiral ganglia, utricle, and organ of Corti-derived progenitors were grown as floating spheres in the absence (controls) or presence of Cr (5 mM) from passage 3 onward. Similarly, dissociated sphere-derived cultures were differentiated for 14 days in the presence or absence of Cr (5 mM) and spiral ganglia sphere-derived cultures in a combination of Cr with the neurotrophin BDNF (50 ng/ml). We found that the cumulative total number of spheres over all passages was significantly higher after Cr supplementation as compared with controls in all the three inner ear cultures. In contrast, sphere sizes were not affected by the administration of Cr. Administration of Cr during differentiation of spiral ganglia cells resulted in a significantly higher density of β-III-tubulin-positive cells compared with controls, whereas densities of myosin VIIa-positive cells in cultures of utricle and organ of Corti were not affected by the treatment. Importantly, a combination of Cr with the neurotrophin BDNF resulted in further significantly increased densities of β-III-tubulin-positive cells in cultures of spiral ganglia cells as compared with single treatments. In sum, Cr promoted continuing propagation of rat inner ear-derived progenitor cells and supported specifically in combination with BDNF the differentiation of neuronal cell types from spiral ganglion

  9. Localization and proteomic characterization of cholesterol-rich membrane microdomains in the inner ear.

    PubMed

    Thomas, Paul V; Cheng, Andrew L; Colby, Candice C; Liu, Liqian; Patel, Chintan K; Josephs, Lydia; Duncan, R Keith

    2014-05-30

    Biological membranes organize and compartmentalize cell signaling into discrete microdomains, a process that often involves stable, cholesterol-rich platforms that facilitate protein-protein interactions. Polarized cells with distinct apical and basolateral cell processes rely on such compartmentalization to maintain proper function. In the cochlea, a variety of highly polarized sensory and non-sensory cells are responsible for the early stages of sound processing in the ear, yet little is known about the mechanisms that traffic and organize signaling complexes within these cells. We sought to determine the prevalence, localization, and protein composition of cholesterol-rich lipid microdomains in the cochlea. Lipid raft components, including the scaffolding protein caveolin and the ganglioside GM1, were found in sensory, neural, and glial cells. Mass spectrometry of detergent-resistant membrane (DRM) fractions revealed over 600 putative raft proteins associated with subcellular localization, trafficking, and metabolism. Among the DRM constituents were several proteins involved in human forms of deafness including those involved in ion homeostasis, such as the potassium channel KCNQ1, the co-transporter SLC12A2, and gap junction proteins GJA1 and GJB6. The presence of caveolin in the cochlea and the abundance of proteins in cholesterol-rich DRM suggest that lipid microdomains play a significant role in cochlear physiology. Although mechanisms underlying cholesterol synthesis, homeostasis, and compartmentalization in the ear are poorly understood, there are several lines of evidence indicating that cholesterol is a key modulator of cochlear function. Depletion of cholesterol in mature sensory cells alters calcium signaling, changes excitability during development, and affects the biomechanical processes in outer hair cells that are responsible for hearing acuity. More recently, we have established that the cholesterol-modulator beta-cyclodextrin is capable of

  10. Magnetic Nanoparticles as Mechanical Actuators of Inner Ear Hair Cells

    DTIC Science & Technology

    2016-01-13

    AFRL-AFOSR-VA-TR-2016-0039 Magnetic nanoparticles as mechanical actuators of inner ear hair cells Dolores Bozovic UNIVERSITY OF CALIFORNIA LOS...4. TITLE AND SUBTITLE Magnetic nanoparticles as mechanical actuators of inner ear hair cells 5a. CONTRACT NUMBER N.A. 5b. GRANT NUMBER FA9550-12...13. SUPPLEMENTARY NOTES 14. ABSTRACT The collaborative project was designed to edevelop the use of magnetic nanoparticles to manipulate auditory hair

  11. Causes and Consequences of Sensory Hair Cell Damage and Recovery in Fishes.

    PubMed

    Smith, Michael E; Monroe, J David

    2016-01-01

    Sensory hair cells are the mechanotransductive receptors that detect gravity, sound, and vibration in all vertebrates. Damage to these sensitive receptors often results in deficits in vestibular function and hearing. There are currently two main reasons for studying the process of hair cell loss in fishes. First, fishes, like other non-mammalian vertebrates, have the ability to regenerate hair cells that have been damaged or lost via exposure to ototoxic chemicals or acoustic overstimulation. Thus, they are used as a biomedical model to understand the process of hair cell death and regeneration and find therapeutics that treat or prevent human hearing loss. Secondly, scientists and governmental natural resource managers are concerned about the potential effects of intense anthropogenic sounds on aquatic organisms, including fishes. Dr. Arthur N. Popper and his students, postdocs and research associates have performed pioneering experiments in both of these lines of fish hearing research. This review will discuss the current knowledge regarding the causes and consequences of both lateral line and inner ear hair cell damage in teleost fishes.

  12. Advances in translational inner ear stem cell research.

    PubMed

    Warnecke, Athanasia; Mellott, Adam J; Römer, Ariane; Lenarz, Thomas; Staecker, Hinrich

    2017-09-01

    Stem cell research is expanding our understanding of developmental biology as well as promising the development of new therapies for a range of different diseases. Within hearing research, the use of stem cells has focused mainly on cell replacement. Stem cells however have a broad range of other potential applications that are just beginning to be explored in the ear. Mesenchymal stem cells are an adult derived stem cell population that have been shown to produce growth factors, modulate the immune system and can differentiate into a wide variety of tissue types. Potential advantages of mesenchymal/adult stem cells are that they have no ethical constraints on their use. However, appropriate regulatory oversight seems necessary in order to protect patients from side effects. Disadvantages may be the lack of efficacy in many preclinical studies. But if proven safe and efficacious, they are easily translatable to clinical trials. The current review will focus on the potential application on mesenchymal stem cells for the treatment of inner ear disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Connecting the ear to the brain: molecular mechanisms of auditory circuit assembly

    PubMed Central

    Appler, Jessica M.; Goodrich, Lisa V.

    2011-01-01

    Our sense of hearing depends on precisely organized circuits that allow us to sense, perceive, and respond to complex sounds in our environment, from music and language to simple warning signals. Auditory processing begins in the cochlea of the inner ear, where sounds are detected by sensory hair cells and then transmitted to the central nervous system by spiral ganglion neurons, which faithfully preserve the frequency, intensity, and timing of each stimulus. During the assembly of auditory circuits, spiral ganglion neurons establish precise connections that link hair cells in the cochlea to target neurons in the auditory brainstem, develop specific firing properties, and elaborate unusual synapses both in the periphery and in the CNS. Understanding how spiral ganglion neurons acquire these unique properties is a key goal in auditory neuroscience, as these neurons represent the sole input of auditory information to the brain. In addition, the best currently available treatment for many forms of deafness is the cochlear implant, which compensates for lost hair cell function by directly stimulating the auditory nerve. Historically, studies of the auditory system have lagged behind other sensory systems due to the small size and inaccessibility of the inner ear. With the advent of new molecular genetic tools, this gap is narrowing. Here, we summarize recent insights into the cellular and molecular cues that guide the development of spiral ganglion neurons, from their origin in the proneurosensory domain of the otic vesicle to the formation of specialized synapses that ensure rapid and reliable transmission of sound information from the ear to the brain. PMID:21232575

  14. Tissue-specific roles of Tbx1 in the development of the outer, middle and inner ear, defective in 22q11DS patients

    PubMed Central

    Arnold, Jelena S.; Braunstein, Evan M.; Ohyama, Takahiro; Groves, Andrew K.; Adams, Joe C.; Brown, M. Christian; Morrow, Bernice E.

    2007-01-01

    Most 22q11.2 deletion syndrome (22q11DS) patients have middle and outer ear anomalies, whereas some have inner ear malformations. Tbx1, a gene hemizygously deleted in 22q11DS patients and required for ear development, is expressed in multiple tissues during embryogenesis. To determine the role of Tbx1 in the first pharyngeal pouch (PPI) in forming outer and middle ears, we tissue-specifically inactivated the gene using Foxg1-Cre. In the conditional mutants, PPI failed to outgrow, preventing the middle ear bone condensations from forming. Tbx1 was also inactivated in the otic vesicle (OV), resulting in the failure of inner ear sensory organ formation, and in duplication of the cochleovestibular ganglion (CVG). Consistent with the anatomical defects, the sensory genes, Otx1 and Bmp4 were downregulated, whereas the CVG genes, Fgf3 and NeuroD, were upregulated. To delineate Tbx1 cell-autonomous roles, a more selective ablation, exclusively in the OV, was performed using Pax2-Cre. In contrast to the Foxg1-Cre mutants, Pax2-Cre conditional mutant mice survived to adulthood and had normal outer and middle ears but had the same inner ear defects as the Tbx1 null mice, with the same gene expression changes. These results demonstrate that Tbx1 has non-cell autonomous roles in PPI in the formation of outer and middle ears and cell-autonomous roles in the OV. Periotic mesenchymal markers, Prx2 and Brn4 were normal in both conditional mutants, whereas they were diminished in Tbx1−/− embryos. Thus, Tbx1 in the surrounding mesenchyme in both sets of conditional mutants cannot suppress the defects in the OV that occur in the null mutants. PMID:16600992

  15. Control of cerebellar granule cell output by sensory-evoked Golgi cell inhibition

    PubMed Central

    Duguid, Ian; Branco, Tiago; Chadderton, Paul; Arlt, Charlotte; Powell, Kate; Häusser, Michael

    2015-01-01

    Classical feed-forward inhibition involves an excitation–inhibition sequence that enhances the temporal precision of neuronal responses by narrowing the window for synaptic integration. In the input layer of the cerebellum, feed-forward inhibition is thought to preserve the temporal fidelity of granule cell spikes during mossy fiber stimulation. Although this classical feed-forward inhibitory circuit has been demonstrated in vitro, the extent to which inhibition shapes granule cell sensory responses in vivo remains unresolved. Here we combined whole-cell patch-clamp recordings in vivo and dynamic clamp recordings in vitro to directly assess the impact of Golgi cell inhibition on sensory information transmission in the granule cell layer of the cerebellum. We show that the majority of granule cells in Crus II of the cerebrocerebellum receive sensory-evoked phasic and spillover inhibition prior to mossy fiber excitation. This preceding inhibition reduces granule cell excitability and sensory-evoked spike precision, but enhances sensory response reproducibility across the granule cell population. Our findings suggest that neighboring granule cells and Golgi cells can receive segregated and functionally distinct mossy fiber inputs, enabling Golgi cells to regulate the size and reproducibility of sensory responses. PMID:26432880

  16. Macrophage migration inhibitory factor acts as a neurotrophin in the developing inner ear.

    PubMed

    Bank, Lisa M; Bianchi, Lynne M; Ebisu, Fumi; Lerman-Sinkoff, Dov; Smiley, Elizabeth C; Shen, Yu-chi; Ramamurthy, Poornapriya; Thompson, Deborah L; Roth, Therese M; Beck, Christine R; Flynn, Matthew; Teller, Ryan S; Feng, Luming; Llewellyn, G Nicholas; Holmes, Brandon; Sharples, Cyrrene; Coutinho-Budd, Jaeda; Linn, Stephanie A; Chervenak, Andrew P; Dolan, David F; Benson, Jennifer; Kanicki, Ariane; Martin, Catherine A; Altschuler, Richard; Koch, Alisa E; Koch, Alicia E; Jewett, Ethan M; Germiller, John A; Barald, Kate F

    2012-12-01

    This study is the first to demonstrate that macrophage migration inhibitory factor (MIF), an immune system 'inflammatory' cytokine that is released by the developing otocyst, plays a role in regulating early innervation of the mouse and chick inner ear. We demonstrate that MIF is a major bioactive component of the previously uncharacterized otocyst-derived factor, which directs initial neurite outgrowth from the statoacoustic ganglion (SAG) to the developing inner ear. Recombinant MIF acts as a neurotrophin in promoting both SAG directional neurite outgrowth and neuronal survival and is expressed in both the developing and mature inner ear of chick and mouse. A MIF receptor, CD74, is found on both embryonic SAG neurons and adult mouse spiral ganglion neurons. Mif knockout mice are hearing impaired and demonstrate altered innervation to the organ of Corti, as well as fewer sensory hair cells. Furthermore, mouse embryonic stem cells become neuron-like when exposed to picomolar levels of MIF, suggesting the general importance of this cytokine in neural development.

  17. ADAM10 and γ-secretase regulate sensory regeneration in the avian vestibular organs.

    PubMed

    Warchol, Mark E; Stone, Jennifer; Barton, Matthew; Ku, Jeffrey; Veile, Rose; Daudet, Nicolas; Lovett, Michael

    2017-08-01

    The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway. The present study examined molecular influences on regeneration in the avian utricle, which has a particularly robust regenerative ability. Chicken utricles were placed in organotypic culture and hair cells were lesioned by application of the ototoxic antibiotic streptomycin. Cultures were then allowed to regenerate in vitro for seven days. Some specimens were treated with small molecule inhibitors of γ-secretase or ADAM10, proteases which are essential for transmission of Notch signaling. As expected, treatment with both inhibitors led to increased numbers of replacement hair cells. However, we also found that inhibition of both proteases resulted in increased regenerative proliferation. Subsequent experiments showed that inhibition of γ-secretase or ADAM10 could also trigger proliferation in undamaged utricles. To better understand these phenomena, we used RNA-Seq profiling to characterize changes in gene expression following γ-secretase inhibition. We observed expression patterns that were consistent with Notch pathway inhibition, but we also found that the utricular sensory epithelium contains numerous γ-secretase substrates that might regulate cell cycle entry and possibly supporting cell-to-hair cell conversion. Together, our data suggest multiple roles for γ-secretase and ADAM10 in vestibular hair cell regeneration. Copyright © 2017. Published by Elsevier Inc.

  18. THE POTENTIAL ROLE OF ENDOGENOUS STEM CELLS IN REGENERATION OF THE INNER EAR

    PubMed Central

    Martinez-Monedero, Rodrigo; Oshima, Kazuo; Heller, Stefan; Edge, Albert S.B.

    2007-01-01

    Stem cells in various mammalian tissues retain the capacity to renew themselves and may be able to restore damaged tissue. Their existence has been proven by genetic tracer studies that demonstrate their differentiation into multiple tissue types and by their ability to self-renew through proliferation. Stem cells from the adult nervous system proliferate to form clonal floating colonies called spheres in vitro, and recent studies have demonstrated sphere formation by cells in the cochlea in addition to the vestibular system and the auditory ganglia, indicating that these tissues contain cells with stem cell properties. The presence of stem cells in the inner ear raises the hope of regeneration of mammalian inner ear cells but is difficult to correlate with the lack spontaneous regeneration seen in the inner ear after tissue damage. Loss of stem cells postnatally in the cochlea may correlate with the loss of regenerative capacity and may limit our ability to stimulate regeneration. Retention of sphere forming capacity in adult vestibular tissues suggests that the limited capacity for repair may be attributed to the continued presence of progenitor cells. Future strategies for regeneration must consider the distribution of endogenous stem cells in the inner ear and whether cells with the capacity for regeneration are retained. PMID:17321086

  19. Sensory Hair Cells: An Introduction to Structure and Physiology.

    PubMed

    McPherson, Duane R

    2018-06-18

    Sensory hair cells are specialized secondary sensory cells that mediate our senses of hearing, balance, linear acceleration, and angular acceleration (head rotation). In addition, hair cells in fish and amphibians mediate sensitivity to water movement through the lateral line system, and closely related electroreceptive cells mediate sensitivity to low-voltage electric fields in the aquatic environment of many fish species and several species of amphibian.Sensory hair cells share many structural and functional features across all vertebrate groups, while at the same time they are specialized for employment in a wide variety of sensory tasks. The complexity of hair cell structure is large, and the diversity of hair cell applications in sensory systems exceeds that seen for most, if not all, sensory cell types. The intent of this review is to summarize the more significant structural features and some of the more interesting and important physiological mechanisms that have been elucidated thus far. Outside vertebrates, hair cells are only known to exist in the coronal organ of tunicates. Electrical resonance, electromotility, and their exquisite mechanical sensitivity all contribute to the attractiveness of hair cells as a research subject.

  20. Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea.

    PubMed

    Chai, Renjie; Kuo, Bryan; Wang, Tian; Liaw, Eric J; Xia, Anping; Jan, Taha A; Liu, Zhiyong; Taketo, Makoto M; Oghalai, John S; Nusse, Roeland; Zuo, Jian; Cheng, Alan G

    2012-05-22

    Inner ear hair cells are specialized sensory cells essential for auditory function. Previous studies have shown that the sensory epithelium is postmitotic, but it harbors cells that can behave as progenitor cells in vitro, including the ability to form new hair cells. Lgr5, a Wnt target gene, marks distinct supporting cell types in the neonatal cochlea. Here, we tested the hypothesis that Lgr5(+) cells are Wnt-responsive sensory precursor cells. In contrast to their quiescent in vivo behavior, Lgr5(+) cells isolated by flow cytometry from neonatal Lgr5(EGFP-CreERT2/+) mice proliferated and formed clonal colonies. After 10 d in culture, new sensory cells formed and displayed specific hair cell markers (myo7a, calretinin, parvalbumin, myo6) and stereocilia-like structures expressing F-actin and espin. In comparison with other supporting cells, Lgr5(+) cells were enriched precursors to myo7a(+) cells, most of which formed without mitotic division. Treatment with Wnt agonists increased proliferation and colony-formation capacity. Conversely, small-molecule inhibitors of Wnt signaling suppressed proliferation without compromising the myo7a(+) cells formed by direct differentiation. In vivo lineage tracing supported the idea that Lgr5(+) cells give rise to myo7a(+) hair cells in the neonatal Lgr5(EGFP-CreERT2/+) cochlea. In addition, overexpression of β-catenin initiated proliferation and led to transient expansion of Lgr5(+) cells within the cochlear sensory epithelium. These results suggest that Lgr5 marks sensory precursors and that Wnt signaling can promote their proliferation and provide mechanistic insights into Wnt-responsive progenitor cells during sensory organ development.

  1. [Lop ear - knife, tape, or nothing at all?].

    PubMed

    Klockars, Tuomas

    2013-01-01

    More than 200 different surgical techniques of correction of lop ear have been published. The operation is usually recommended to be performed at the age of six years or after. In addition, lop ear surgery involves risks, the most common complications being bleeding, infections, sensory alterations and scarring problems. Surgical preference and decision should always be based on realistic expectations of the patient or the parents, and prior to the decision they should have adequate information about the nature of the procedure and potential complications. Splint therapy of lop ear is possible for infants.

  2. Hair cell regeneration in the chick inner ear following acoustic trauma: ultrastructural and immunohistochemical studies.

    PubMed

    Umemoto, M; Sakagami, M; Fukazawa, K; Ashida, K; Kubo, T; Senda, T; Yoneda, Y

    1995-09-01

    The regeneration of hair cells in the chick inner ear following acoustic trauma was examined using transmission electron microscopy. In addition, the localization of proliferation cell nuclear antigen (PCNA) and basic fibroblast growth factor (b-FGF) was demonstrated immunohistochemically. The auditory sensory epithelium of the normal chick consists of short and tall hair cells and supporting cells. Immediately after noise exposure to a 1500-Hz pure tone at a sound pressure level of 120 decibels for 48 h, all the short hair cells disappeared in the middle region of the auditory epithelium. Twelve hours to 1 day after exposure, mitotic cells, binucleate cells and PCNA-positive supporting cells were observed, and b-FGF immunoreactivity was shown in the supporting cells and glial cells near the habenula perforata. Spindle-shaped hair cells with immature stereocilia and a kinocilium appeared 3 days after exposure; these cells had synaptic connections with the newly developed nerve endings. The spindle-shaped hair cell is considered to be a transitional cell in the lineage of the supporting cell to the mature short hair cell. These results indicate that, after acoustic trauma, the supporting cells divide and differentiate into new short hair cells via spindle-shaped hair cells. Furthermore, it is suggested that b-FGF is related to the proliferation of the supporting cells and the extension of the nerve fibers.

  3. Gene Expression by Mouse Inner Ear Hair Cells during Development

    PubMed Central

    Scheffer, Déborah I.; Shen, Jun

    2015-01-01

    Hair cells of the inner ear are essential for hearing and balance. As a consequence, pathogenic variants in genes specifically expressed in hair cells often cause hereditary deafness. Hair cells are few in number and not easily isolated from the adjacent supporting cells, so the biochemistry and molecular biology of hair cells can be difficult to study. To study gene expression in hair cells, we developed a protocol for hair cell isolation by FACS. With nearly pure hair cells and surrounding cells, from cochlea and utricle and from E16 to P7, we performed a comprehensive cell type-specific RNA-Seq study of gene expression during mouse inner ear development. Expression profiling revealed new hair cell genes with distinct expression patterns: some are specific for vestibular hair cells, others for cochlear hair cells, and some are expressed just before or after maturation of mechanosensitivity. We found that many of the known hereditary deafness genes are much more highly expressed in hair cells than surrounding cells, suggesting that genes preferentially expressed in hair cells are good candidates for unknown deafness genes. PMID:25904789

  4. Tympanal mechanics and neural responses in the ears of a noctuid moth

    NASA Astrophysics Data System (ADS)

    Ter Hofstede, Hannah M.; Goerlitz, Holger R.; Montealegre-Z, Fernando; Robert, Daniel; Holderied, Marc W.

    2011-12-01

    Ears evolved in many groups of moths to detect the echolocation calls of predatory bats. Although the neurophysiology of bat detection has been intensively studied in moths for decades, the relationship between sound-induced movement of the noctuid tympanic membrane and action potentials in the auditory sensory cells (A1 and A2) has received little attention. Using laser Doppler vibrometry, we measured the velocity and displacement of the tympanum in response to pure tone pulses for moths that were intact or prepared for neural recording. When recording from the auditory nerve, the displacement of the tympanum at the neural threshold remained constant across frequencies, whereas velocity varied with frequency. This suggests that the key biophysical parameter for triggering action potentials in the sensory cells of noctuid moths is tympanum displacement, not velocity. The validity of studies on the neurophysiology of moth hearing rests on the assumption that the dissection and recording procedures do not affect the biomechanics of the ear. There were no consistent differences in tympanal velocity or displacement when moths were intact or prepared for neural recordings for sound levels close to neural threshold, indicating that this and other neurophysiological studies provide good estimates of what intact moths hear at threshold.

  5. Expression of Prox1 defines regions of the avian otocyst that give rise to sensory or neural cells

    NASA Technical Reports Server (NTRS)

    Stone, Jennifer S.; Shang, Jia-Lin; Tomarev, Stanislav

    2003-01-01

    The simple primordium of the inner ear (otocyst) differentiates into many cell types, including sensory neurons and hair cells. We examined expression of the divergent homeobox transcription factor, cProx1, during otocyst development in chickens. Nuclear cProx1 protein is not evident in the otic placode but emerges in the otic cup by stage 12. At stage 16, cProx1-positive nuclei are scattered continuously throughout the neuroepithelium, from anteroventral to posteromedial. These labeled cells are neural precursors; they express betaIII-tubulin and migrate to the cochleovestibular ganglion between stages 13 and 21. By stage 18, two areas develop a dense pattern of cProx1 expression in which every nucleus is labeled. These areas emerge at the anterior and posterior extremes of the band of scattered cProx1 expression and express the sensory markers cSerrate1 and Cath1 by stage 23. Four discrete patches of dense cProx1 expression appear by stage 23 that correspond to the future superior crista, lateral crista, saccular macula, and posterior crista, as confirmed by immunolabeling for hair cell antigen (HCA) by stage 29. The remaining sensory epithelia display a dense pattern of cProx1 expression and label for HCA by stage 29. In the basilar papilla, nuclear cProx1 expression is down-regulated in most hair cells by stage 37 and in many supporting cells by stage 40. Our findings show that regions of the otocyst that give rise to neurons or hair cells are distinguished by their relative density of cProx1-positive nuclei, and suggest a role for cProx1 in the genesis of these cell types.

  6. Gfi1-Cre knock-in mouse line: A tool for inner ear hair cell-specific gene deletion

    PubMed Central

    Yang, Hua; Gan, Jean; Xie, Xiaoling; Deng, Min; Feng, Liang; Chen, Xiaowei; Gao, Zhiqiang; Gan, Lin

    2010-01-01

    Summary Gfi1encodes a zinc-finger transcription factor essential for the development and maintenance of haematopoiesis and the inner ear. In mouse inner ear, Gfi1 expression is confined to hair cells during development and in adulthood. To construct a genetic tool for inner ear hair cell-specific gene deletion, we generated a Gfi1-Cre mouse line by knocking-in Cre coding sequences into the Gfi1 locus and inactivating the endogenous Gfi1. The specificity and efficiency of Gfi1-Cre recombinase-mediated recombination in the developing inner ear was revealed through the expression of the conditional R26R-lacZ reporter gene. The onset of lacZ expression in the Gfi1Cre/+ inner ear was first detected at E13.5 in the vestibule and at E15.5 in the cochlea, coinciding with the generation of hair cells. Throughout inner ear development, lacZ expression was detected only in hair cells. Thus, Gfi1-Cre knock-in mouse line provides a useful tool for gene manipulations specifically in inner ear hair cells. PMID:20533399

  7. Expression of the mouse Macf2 gene during inner ear development.

    PubMed

    Leonova, Elena V; Lomax, Margaret I

    2002-09-30

    Plakins, a family of linker proteins that connect cytoskeletal elements to cellular junctions and the extracellular matrix, are primarily responsible for the mechanical properties of cells and tissues. They include desmoplakin, envoplakin, plectin, dystonin/BPAG1, and Kakapo. Mutations in plakins cause several skin, muscular and neurological disorders. Macrophins are a recently discovered subfamily of plakins with binding domains for actin, intermediate filaments and microtubules. Characteristic features of macrophins include variable actin binding domains, a central rod domain containing both plectin and spectrin repeats, and a C-terminus containing EF hands and GAS2/GAR22 domain. We have examined expression of mouse Macf2, encoding macrophin-2, in adult tissues and in the developing, neonatal, and mature inner ear by in situ hybridization. Northern blot analysis identified three large tissue-specific Macf2 transcripts: a 16-kb mRNA in skeletal muscle and heart, a 15-kb mRNA in brain, and a 9-kb mRNA in RNA from ovary plus uterus. In situ hybridization of the developing mouse inner ear indicated that Macf2 is expressed in the otocyst at day 12.5, in the sensory epithelium by embryonic day 16.5, and in both inner and outer hair cells by day 16.5. Macf2 is expressed in the bodies of both sensory and motor neurons in the central and peripheral nervous system, including the auditory pathway. The Macf2 protein could be involved in the regulation of cytoskeletal connections to cellular junctions and play an important structural role in organs, such as the inner ear, that are subjected to strong mechanical forces. Copyright 2002 Elsevier Science B.V.

  8. DNA damage signaling regulates age-dependent proliferative capacity of quiescent inner ear supporting cells

    PubMed Central

    Laos, Maarja; Anttonen, Tommi; Kirjavainen, Anna; Hällström, Taija af; Laiho, Marikki; Pirvola, Ulla

    2014-01-01

    Supporting cells (SCs) of the cochlear (auditory) and vestibular (balance) organs hold promise as a platform for therapeutic regeneration of the sensory hair cells. Prior data have shown proliferative restrictions of adult SCs forced to re-enter the cell cycle. By comparing juvenile and adult SCs in explant cultures, we have here studied how proliferative restrictions are linked with DNA damage signaling. Cyclin D1 overexpression, used to stimulate cell cycle re-entry, triggered higher proliferative activity of juvenile SCs. Phosphorylated form of histone H2AX (γH2AX) and p53 binding protein 1 (53BP1) were induced in a foci-like pattern in SCs of both ages as an indication of DNA double-strand break formation and activated DNA damage response. Compared to juvenile SCs, γH2AX and the repair protein Rad51 were resolved with slower kinetics in adult SCs, accompanied by increased apoptosis. Consistent with the in vitro data, in a Rb mutant mouse model in vivo, cell cycle re-entry of SCs was associated with γH2AX foci induction. In contrast to cell cycle reactivation, pharmacological stimulation of SC-to-hair-cell transdifferentiation in vitro did not trigger γH2AX. Thus, DNA damage and its prolonged resolution are critical barriers in the efforts to stimulate proliferation of the adult inner ear SCs. PMID:25063730

  9. Developing an Ear Prosthesis Fabricated in Polyvinylidene Fluoride by a 3D Printer with Sensory Intrinsic Properties of Pressure and Temperature

    PubMed Central

    Suaste-Gómez, Ernesto; Rodríguez-Roldán, Grissel; Reyes-Cruz, Héctor; Terán-Jiménez, Omar

    2016-01-01

    An ear prosthesis was designed in 3D computer graphics software and fabricated using a 3D printing process of polyvinylidene fluoride (PVDF) for use as a hearing aid. In addition, the prosthesis response to pressure and temperature was observed. Pyroelectric and piezoelectric properties of this ear prosthesis were investigated using an astable multivibrator circuit, as changes in PVDF permittivity were observed according to variations of pressure and temperature. The results show that this prosthesis is reliable for use under different conditions of pressure (0 Pa to 16,350 Pa) and temperature (2 °C to 90 °C). The experimental results show an almost linear and inversely proportional behavior between the stimuli of pressure and temperature with the frequency response. This 3D-printed ear prosthesis is a promising tool and has a great potentiality in the biomedical engineering field because of its ability to generate an electrical potential proportional to pressure and temperature, and it is the first time that such a device has been processed by the additive manufacturing process (3D printing). More work needs to be carried out to improve the performance, such as electrical stimulation of the nervous system, thereby extending the purpose of a prosthesis to the area of sensory perception. PMID:26959026

  10. Developing an Ear Prosthesis Fabricated in Polyvinylidene Fluoride by a 3D Printer with Sensory Intrinsic Properties of Pressure and Temperature.

    PubMed

    Suaste-Gómez, Ernesto; Rodríguez-Roldán, Grissel; Reyes-Cruz, Héctor; Terán-Jiménez, Omar

    2016-03-04

    An ear prosthesis was designed in 3D computer graphics software and fabricated using a 3D printing process of polyvinylidene fluoride (PVDF) for use as a hearing aid. In addition, the prosthesis response to pressure and temperature was observed. Pyroelectric and piezoelectric properties of this ear prosthesis were investigated using an astable multivibrator circuit, as changes in PVDF permittivity were observed according to variations of pressure and temperature. The results show that this prosthesis is reliable for use under different conditions of pressure (0 Pa to 16,350 Pa) and temperature (2 °C to 90 °C). The experimental results show an almost linear and inversely proportional behavior between the stimuli of pressure and temperature with the frequency response. This 3D-printed ear prosthesis is a promising tool and has a great potentiality in the biomedical engineering field because of its ability to generate an electrical potential proportional to pressure and temperature, and it is the first time that such a device has been processed by the additive manufacturing process (3D printing). More work needs to be carried out to improve the performance, such as electrical stimulation of the nervous system, thereby extending the purpose of a prosthesis to the area of sensory perception.

  11. Histone Deacetylase Inhibitor Induces the Expression of Select Epithelial Genes in Mouse Utricle Sensory Epithelia-Derived Progenitor Cells

    PubMed Central

    Wang, Jue

    2014-01-01

    Abstract Mouse utricle sensory epithelial cell–derived progenitor cells (MUCs), which have hair cell progenitor and mesenchymal features via epithelial-to-mesenchymal transition (EMT) as previously described, provide a potential approach for hair cell regeneration via cell transplantation. In this study, we treated MUCs with trichostatin A (TSA) to determine whether histone deacetylase inhibitor is able to stimulate the expression of epithelial genes in MUCs, an essential step for guiding mesenchymal-like MUCs to become sensory epithelial cells. After 72 h of TSA treatment, MUCs acquired epithelial-like features, which were indicated by increased expression of epithelial markers such as Cdh1, Krt18, and Dsp. Additionally, TSA decreased the expression of mesenchymal markers, including Zeb1, Zeb2, Snai1, and Snai2, and prosensory genes Lfng, Six1, and Dlx5. Moreover, the expression of the hair cell genes Atoh1 and Myo6 was increased in TSA-treated MUCs. We also observed significantly decreased expression of Hdac2 and Hdac3 in TSA-treated MUCs. However, no remarkable change was detected in protein expression using immunofluorescence, indicating that TSA-induced HDAC inhibition may contribute to the initial stage of the mesenchymal-to-epithelial phenotypic change. In the future, more work is needed to induce hair cell regeneration using inner ear tissue–derived progenitors to achieve an entire mesenchymal-to-epithelial transition. PMID:24945595

  12. The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15.

    PubMed

    Ahmed, Zubair M; Goodyear, Richard; Riazuddin, Saima; Lagziel, Ayala; Legan, P Kevin; Behra, Martine; Burgess, Shawn M; Lilley, Kathryn S; Wilcox, Edward R; Riazuddin, Sheikh; Griffith, Andrew J; Frolenkov, Gregory I; Belyantseva, Inna A; Richardson, Guy P; Friedman, Thomas B

    2006-06-28

    Sound and acceleration are detected by hair bundles, mechanosensory structures located at the apical pole of hair cells in the inner ear. The different elements of the hair bundle, the stereocilia and a kinocilium, are interconnected by a variety of link types. One of these links, the tip link, connects the top of a shorter stereocilium with the lateral membrane of an adjacent taller stereocilium and may gate the mechanotransducer channel of the hair cell. Mass spectrometric and Western blot analyses identify the tip-link antigen, a hitherto unidentified antigen specifically associated with the tip and kinocilial links of sensory hair bundles in the inner ear and the ciliary calyx of photoreceptors in the eye, as an avian ortholog of human protocadherin-15, a product of the gene for the deaf/blindness Usher syndrome type 1F/DFNB23 locus. Multiple protocadherin-15 transcripts are shown to be expressed in the mouse inner ear, and these define four major isoform classes, two with entirely novel, previously unidentified cytoplasmic domains. Antibodies to the three cytoplasmic domain-containing isoform classes reveal that each has a different spatiotemporal expression pattern in the developing and mature inner ear. Two isoforms are distributed in a manner compatible for association with the tip-link complex. An isoform located at the tips of stereocilia is sensitive to calcium chelation and proteolysis with subtilisin and reappears at the tips of stereocilia as transduction recovers after the removal of calcium chelators. Protocadherin-15 is therefore associated with the tip-link complex and may be an integral component of this structure and/or required for its formation.

  13. Squamous cell carcinoma and consequent otitis in a Long-eared Hedgehog (Hemiechinus auritus)--case report.

    PubMed

    Gál, Janos; Landauer, Krisztina; Palade, Elena Alina; Ivaskevics, Katalin; Rusvai, Miklós; Demeter, Zoltán

    2009-03-01

    The authors describe a squamous cell carcinoma arising from the ear canal of a Long-eared Hedgehog (Hemiechinus auritus). No metastasis could be identified elsewhere in the animal. Due to the irritation caused by the tumorous proliferation the animal constantly scratched the affected area, which led to secondary bacterial infection of the middle ear accompanied by the stagnation of an increased volume of local secretions. Using routine haematoxylin and eosin and immunohistochemical staining techniques, the tumour was identified as a squamous cell carcinoma. This work constitutes the first description of such a tumour in a Long-eared Hedgehog.

  14. miR-124 promotes the neuronal differentiation of mouse inner ear neural stem cells

    PubMed Central

    Jiang, Di; Du, Jintao; Zhang, Xuemei; Zhou, Wei; Zong, Lin; Dong, Chang; Chen, Kaitian; Chen, Yu; Chen, Xihui; Jiang, Hongyan

    2016-01-01

    MicroRNAs (miRNAs or miRs) act as key regulators in neuronal development, synaptic morphogenesis and plasticity. However, their role in the neuronal differentiation of inner ear neural stem cells (NSCs) remains unclear. In this study, 6 miRNAs were selected and their expression patterns during the neuronal differentiation of inner ear NSCs were examined by RT-qPCR. We demonstrated that the culture of spiral ganglion stem cells present in the inner ears of newborn mice gave rise to neurons in vitro. The expression patterns of miR-124, miR-132, miR-134, miR-20a, miR-17-5p and miR-30a-5p were examined during a 14-day neuronal differentiation period. We found that miR-124 promoted the neuronal differentiation of and neurite outgrowth in mouse inner ear NSCs, and that the changes in the expression of tropomyosin receptor kinase B (TrkB) and cell division control protein 42 homolog (Cdc42) during inner ear NSC differentiation were associated with miR-124 expression. Our findings indicate that miR-124 plays a role in the neuronal differentiation of inner ear NSCs. This finding may lead to the development of novel strategies for restoring hearing in neurodegenerative diseases. PMID:28025992

  15. Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome

    PubMed Central

    Hurd, Elizabeth A.; Adams, Meredith E.; Layman, Wanda S.; Swiderski, Donald L.; Beyer, Lisa A.; Halsey, Karin E.; Benson, Jennifer M.; Gong, Tzy-Wen; Dolan, David F.; Raphael, Yehoash; Martin, Donna M.

    2011-01-01

    Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression in mature middle and inner ears, analyzed morphological features of mutant ears and tested whether Chd7 mutant mice have altered responses to noise exposure and correlated those responses to inner and middle ear structure. We found that Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles. There were no obvious defects in individual hair cell morphology by Prestin immunostaining or scanning electron microscopy, and cochlear innervation appeared normal in Chd7Gt/+ mice. Hearing thresholds by auditory brainstem response (ABR) testing were elevated at 4 and 16 kHz in Chd7Gt/+ mice, and there were reduced distortion product otoacoustic emissions (DPOAE). Exposure of Chd7Gt/+ mice to broadband noise resulted in variable degrees of hair cell loss which inversely correlated with severity of stapedial defects. The degrees of hair cell loss and threshold shifts after noise exposure were more severe in wild type mice than in mutants. Together, these data indicate that Chd7Gt/+ mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears. PMID:21875659

  16. Functional evaluation of a cell replacement therapy in the inner ear

    PubMed Central

    Hu, Zhengqing; Ulfendahl, Mats; Prieskorn, Diane M.; Olivius, N. Petri; Miller, Josef M.

    2015-01-01

    Hypothesis Cell replacement therapy in the inner ear will contribute to the functional recovery of hearing loss. Background Cell replacement therapy is a potentially powerful approach to replace degenerated or severely damaged spiral ganglion neurons. This study aimed at stimulating the neurite outgrowth of the implanted neurons and enhancing the potential therapeutic of inner ear cell implants. Methods Chronic electrical stimulation (CES) and exogenous neurotrophic growth factor (NGF) were applied to 46 guinea pigs transplanted with embryonic dorsal root ganglion (DRG) neurons four days post deafening. The animals were evaluated with the electrically-evoked auditory brain stem responses (EABRs) at experimental day 7, 11, 17, 24, 31. The animals were euthanized at day 31 and the inner ears were dissected out for immunohistochemistry investigation. Results Implanted DRG cells, identified by EGFP fluorescence and a neuronal marker, were found close to Rosenthal's canal in the adult inner ear for up to four weeks following transplantation. Extensive neurite projections clearly, greater than in non-treated animals, were observed to penetrate the bony modiolus and reach the spiral ganglion region in animals supplied with CES and/or NGF. There was, however, no significant difference in the thresholds of EABRs between DRG-transplanted-animals supplied with CES and/or NGF and DRG-transplanted animals without CES or NGF supplement. Conclusions The results suggest that CES and/or NGF can stimulate neurite outgrowth from implanted neurons, although based on EABR measurement these interventions did not induce functional connections to the central auditory pathway. Additional time or novel approaches may enhance functional responsiveness of implanted cells in the adult cochlea. PMID:19395986

  17. Targeted Deletion of Sox10 by Wnt1-cre Defects Neuronal Migration and Projection in the Mouse Inner Ear

    PubMed Central

    Mao, YanYan; Reiprich, Simone; Wegner, Michael; Fritzsch, Bernd

    2014-01-01

    Sensory nerves of the brainstem are mostly composed of placode-derived neurons, neural crest-derived neurons and neural crest-derived Schwann cells. This mixed origin of cells has made it difficult to dissect interdependence for fiber guidance. Inner ear-derived neurons are known to connect to the brain after delayed loss of Schwann cells in ErbB2 mutants. However, the ErbB2 mutant related alterations in the ear and the brain compound interpretation of the data. We present here a new model to evaluate exclusively the effect of Schwann cell loss on inner ear innervation. Conditional deletion of the neural crest specific transcription factor, Sox10, using the rhombic lip/neural crest specific Wnt1-cre driver spares Sox10 expression in the ear. We confirm that neural crest-derived cells provide a stop signal for migrating spiral ganglion neurons. In the absence of Schwann cells, spiral ganglion neurons migrate into the center of the cochlea and even out of the ear toward the brain. Spiral ganglion neuron afferent processes reach the organ of Corti, but many afferent fibers bypass the organ of Corti to enter the lateral wall of the cochlea. In contrast to this peripheral disorganization, the central projection to cochlear nuclei is normal. Compared to ErbB2 mutants, conditional Sox10 mutants have limited cell death in spiral ganglion neurons, indicating that the absence of Schwann cells alone contributes little to the embryonic survival of neurons. These data suggest that neural crest-derived cells are dispensable for all central and some peripheral targeting of inner ear neurons. However, Schwann cells provide a stop signal for migratory spiral ganglion neurons and facilitate proper targeting of the organ of Corti by spiral ganglion afferents. PMID:24718611

  18. Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

    PubMed

    Mizuno, Mitsuru; Kobayashi, Shinji; Takebe, Takanori; Kan, Hiroomi; Yabuki, Yuichiro; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Nakabayashi, Seiichiro; Ik, Lee Jeong; Maegawa, Jiro; Taniguchi, Hideki

    2014-03-01

    In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies. © AlphaMed Press.

  19. Probing the Xenopus laevis inner ear transcriptome for biological function

    PubMed Central

    2012-01-01

    Background The senses of hearing and balance depend upon mechanoreception, a process that originates in the inner ear and shares features across species. Amphibians have been widely used for physiological studies of mechanotransduction by sensory hair cells. In contrast, much less is known of the genetic basis of auditory and vestibular function in this class of animals. Among amphibians, the genus Xenopus is a well-characterized genetic and developmental model that offers unique opportunities for inner ear research because of the amphibian capacity for tissue and organ regeneration. For these reasons, we implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis. Results Microarray analysis uncovered genes within the X. laevis inner ear transcriptome associated with inner ear function and impairment in other organisms, thereby supporting the inclusion of Xenopus in cross-species genetic studies of the inner ear. The use of gene categories (inner ear tissue; deafness; ion channels; ion transporters; transcription factors) facilitated the assignment of functional significance to probe set identifiers. We enhanced the biological relevance of our microarray data by using a variety of curation approaches to increase the annotation of the Affymetrix GeneChip® Xenopus laevis Genome array. In addition, annotation analysis revealed the prevalence of inner ear transcripts represented by probe set identifiers that lack functional characterization. Conclusions We identified an abundance of targets for genetic analysis of auditory and vestibular function. The orthologues to human genes with known inner ear function and the highly expressed transcripts that lack annotation are particularly interesting candidates for future analyses. We used informatics approaches to impart biologically relevant information to the Xenopus inner ear transcriptome, thereby addressing the

  20. Functional morphology of the inner ear and underwater audiograms of Proteus anguinus (Amphibia, Urodela).

    PubMed

    Bulog, B; Schlegel, P

    2000-01-01

    Octavolateral sensory organs (auditory and lateral line organs) of cave salamander Proteus anguinus are highly differentiated. In the saccular macula of the inner ear the complex pattern of hair cell orientation and the large otoconial mass enable particle displacement direction detection. Additionally, the same organ, through air cavities within the body, enables detection of underwater sound pressure changes thus acting as a hearing organ. The cavities in the lungs and mouth of Proteus are a resonators that transmit underwater sound pressure to the inner ear. Behaviourally determined audiograms indicate hearing sensitivity of 60 dB (rel. 1 microPa) at frequencies between 1 and 10 kHz. The hearing frequency range was between 10 Hz and 10 kHz. The hearing sensitivities of depigmented Proteus and black Proteus were compared. The highest sensitivities of the depigmented animals (N=4) were at frequencies 1.3-1.7 kHz and it was 2 kHz in black animals (N=1). Excellent underwater hearing abilities of Proteus are sensory adaptations to cave habitat.

  1. Ear Deformations Give Bats a Physical Mechanism for Fast Adaptation of Ultrasonic Beam Patterns

    NASA Astrophysics Data System (ADS)

    Gao, Li; Balakrishnan, Sreenath; He, Weikai; Yan, Zhen; Müller, Rolf

    2011-11-01

    A large number of mammals, including humans, have intricate outer ear shapes that diffract incoming sound in a direction- and frequency-specific manner. Through this physical process, the outer ear shapes encode sound-source information into the sensory signals from each ear. Our results show that horseshoe bats could dynamically control these diffraction processes through fast nonrigid ear deformations. The bats’ ear shapes can alter between extreme configurations in about 100 ms and thereby change their acoustic properties in ways that would suit different acoustic sensing tasks.

  2. Hair cell specific NTPDase6 immunolocalisation in vestibular end organs: potential role of purinergic signaling in vestibular sensory transduction.

    PubMed

    O'Keeffe, Mary G; Thorne, Peter R; Housley, Gary D; Robson, Simon C; Vlajkovic, Srdjan M

    2012-01-01

    A complex extracellular nucleotide signalling system acting on P2 receptors is involved in regulation of cochlear function in the mammalian inner ear. Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) are ectonucleotidases that regulate P2 receptor signalling pathways in mammalian tissues by hydrolysing extracellular nucleotides to the respective nucleosides. All enzymes from the CD39/ENTPD family (NTPDase1-8) are expressed in the adult rat cochlea, but their expression and distribution in the vestibular end organ is unknown. This report demonstrates selective expression of NTPDase6 by rat vestibular hair cells. Hair cells transducing both angular acceleration (crista ampullaris) and static head position (maculae of the utricle and saccule) exhibited strong immunolabelling with a bias towards the sensory pole and in particular, the hair cell bundle. NTPDase6 is an intracellular enzyme that can be released in a soluble form from cell cultures and shows an enzymatic preference for nucleoside 5'-diphosphates, such as guanosine 5'-diphosphate (GDP) and uridine 5'-diphosphate (UDP). The main function of NTPDase6 may be the regulation of nucleotide levels in cellular organelles by regulating the conversion of nucleotides to nucleosides. NTPDase6 immunolocalisation in the vestibular end organ could be linked to the regulation of P2 receptor signalling and sensory transduction, including maintenance of vestibular hair bundles.

  3. Inner ear development: building a spiral ganglion and an organ of Corti out of unspecified ectoderm.

    PubMed

    Fritzsch, Bernd; Pan, Ning; Jahan, Israt; Elliott, Karen L

    2015-07-01

    The mammalian inner ear develops from a placodal thickening into a complex labyrinth of ducts with five sensory organs specialized to detect position and movement in space. The mammalian ear also develops a spiraled cochlear duct containing the auditory organ, the organ of Corti (OC), specialized to translate sound into hearing. Development of the OC from a uniform sheet of ectoderm requires unparalleled precision in the topological developmental engineering of four different general cell types, namely sensory neurons, hair cells, supporting cells, and general otic epithelium, into a mosaic of ten distinctly recognizable cell types in and around the OC, each with a unique distribution. Moreover, the OC receives unique innervation by ear-derived spiral ganglion afferents and brainstem-derived motor neurons as efferents and requires neural-crest-derived Schwann cells to form myelin and neural-crest-derived cells to induce the stria vascularis. This transformation of a sheet of cells into a complicated interdigitating set of cells necessitates the orchestrated expression of multiple transcription factors that enable the cellular transformation from ectoderm into neurosensory cells forming the spiral ganglion neurons (SGNs), while simultaneously transforming the flat epithelium into a tube, the cochlear duct, housing the OC. In addition to the cellular and conformational changes forming the cochlear duct with the OC, changes in the surrounding periotic mesenchyme form passageways for sound to stimulate the OC. We review molecular developmental data, generated predominantly in mice, in order to integrate the well-described expression changes of transcription factors and their actions, as revealed in mutants, in the formation of SGNs and OC in the correct position and orientation with suitable innervation. Understanding the molecular basis of these developmental changes leading to the formation of the mammalian OC and highlighting the gaps in our knowledge might guide in

  4. Inner ear development: Building a spiral ganglion and an organ of Corti out of unspecified ectoderm

    PubMed Central

    Fritzsch, Bernd; Pan, Ning; Jahan, Israt; Elliott, Karen L.

    2014-01-01

    The mammalian inner ear develops from a placodal thickening into a complex labyrinth of ducts with five sensory organs specialized to detect position and movement in space. In addition, the mammalian ear develops a spiraled cochlear duct containing the auditory organ, the organ of Corti (OC), specialized to translate sound into hearing. Developing the OC out of a uniform sheet of ectoderm requires an unparalleled precision in topological developmental engineering of four different general cell types, sensory neurons, hair cells, supporting cells, and general otic epithelium, into a mosaic of ten distinctly recognizable cell types in and around the OC, each with a unique distribution. In addition, the OC receives a unique innervation by ear-derived spiral ganglion afferents and brainstem-derived motor neurons as efferents, and requires neural crest-derived Schwann cells to form myelin and neural crest-derived cells to induce the stria vascularis. To achieve this transformation of a sheet of cells into a complicated interdigitating set of cells necessitates the orchestrated expression of multiple transcription factors that enable the cellular transformation from ectoderm into neurosensory cells forming the spiral ganglion neurons (SGN) while simultaneously transforming the flat epithelium into a tube, the cochlear duct housing the OC. In addition to the cellular and conformational changes to make the cochlear duct with the OC, additional changes in the surrounding periotic mesenchyme form passageways for sound to stimulate the OC. This article reviews molecular developmental data generated predominantly in mice. The available data are ordered into a plausible scenario that integrates the well described expression changes of transcription factors and their actions revealed in mouse mutants for formation of SGNs and OC in the right position and orientation with the right kind of innervation. Understanding the molecular basis of these developmental changes leading to

  5. Isolating LacZ-expressing cells from mouse inner ear tissues using flow cytometry.

    PubMed

    Jan, Taha A; Chai, Renjie; Sayyid, Zahra N; Cheng, Alan G

    2011-12-23

    Isolation of specific cell types allows one to analyze rare cell populations such as stem/progenitor cells. Such an approach to studying inner ear tissues presents a unique challenge because of the paucity of cells of interest and few transgenic reporter mouse models. Here, we describe a protocol using fluorescence-conjugated probes to selectively label LacZ-positive cells from the neonatal cochleae. The most common underlying pathology of sensorineural hearing loss is the irreversible damage and loss of cochlear sensory hair cells, which are required to transduce sound waves to neural impulses. Recent evidence suggests that the murine auditory and vestibular organs harbor stem/progenitor cells that may have regenerative potential. These findings warrant further investigation, including identifying specific cell types with stem/progenitor cell characteristics. The Wnt signaling pathway has been demonstrated to play a critical role in maintaining stem/progenitor cell populations in several organ systems. We have recently identified Wnt-responsive Axin2-expressing cells in the neonatal cochlea, but their function is largely unknown. To better understand the behavior of these Wnt-responsive cells in vitro, we have developed a method of isolating Axin2-expressing cells from cochleae of Axin2-LacZ reporter mice. Using flow cytometry to isolate Axin2-LacZ positive cells from the neonatal cochleae, we could in turn execute a variety of experiments on live cells to interrogate their behavior as stem/progenitor cells. Here, we describe in detail the steps for the microdissection of neonatal cochlea, dissociation of these tissues, labeling of the LacZ-positive cells using a fluorogenic substrate, and cell sorting. Techniques for dissociating cochleae into single cells and isolating cochlear cells via flow cytometry have been described. We have made modifications to these techniques to establish a novel protocol to isolate LacZ-expressing cells from the neonatal cochlea.

  6. Think like a sponge: The genetic signal of sensory cells in sponges.

    PubMed

    Mah, Jasmine L; Leys, Sally P

    2017-11-01

    A complex genetic repertoire underlies the apparently simple body plan of sponges. Among the genes present in poriferans are those fundamental to the sensory and nervous systems of other animals. Sponges are dynamic and sensitive animals and it is intuitive to link these genes to behaviour. The proposal that ctenophores are the earliest diverging metazoan has led to the question of whether sponges possess a 'pre-nervous' system or have undergone nervous system loss. Both lines of thought generally assume that the last common ancestor of sponges and eumetazoans possessed the genetic modules that underlie sensory abilities. By corollary extant sponges may possess a sensory cell homologous to one present in the last common ancestor, a hypothesis that has been studied by gene expression. We have performed a meta-analysis of all gene expression studies published to date to explore whether gene expression is indicative of a feature's sensory function. In sponges we find that eumetazoan sensory-neural markers are not particularly expressed in structures with known sensory functions. Instead it is common for these genes to be expressed in cells with no known or uncharacterized sensory function. Indeed, many sensory-neural markers so far studied are expressed during development, perhaps because many are transcription factors. This suggests that the genetic signal of a sponge sensory cell is dissimilar enough to be unrecognizable when compared to a bilaterian sensory or neural cell. It is possible that sensory-neural markers have as yet unknown functions in sponge cells, such as assembling an immunological synapse in the larval globular cell. Furthermore, the expression of sensory-neural markers in non-sensory cells, such as adult and larval epithelial cells, suggest that these cells may have uncharacterized sensory functions. While this does not rule out the co-option of ancestral sensory modules in later evolving groups, a distinct genetic foundation may underlie the

  7. Natural Bizbenzoquinoline Derivatives Protect Zebrafish Lateral Line Sensory Hair Cells from Aminoglycoside Toxicity.

    PubMed

    Kruger, Matthew; Boney, Robert; Ordoobadi, Alexander J; Sommers, Thomas F; Trapani, Josef G; Coffin, Allison B

    2016-01-01

    Moderate to severe hearing loss affects 360 million people worldwide and most often results from damage to sensory hair cells. Hair cell damage can result from aging, genetic mutations, excess noise exposure, and certain medications including aminoglycoside antibiotics. Aminoglycosides are effective at treating infections associated with cystic fibrosis and other life-threatening conditions such as sepsis, but cause hearing loss in 20-30% of patients. It is therefore imperative to develop new therapies to combat hearing loss and allow safe use of these potent antibiotics. We approach this drug discovery question using the larval zebrafish lateral line because zebrafish hair cells are structurally and functionally similar to mammalian inner ear hair cells and respond similarly to toxins. We screened a library of 502 natural compounds in order to identify novel hair cell protectants. Our screen identified four bisbenzylisoquinoline derivatives: berbamine, E6 berbamine, hernandezine, and isotetrandrine, each of which robustly protected hair cells from aminoglycoside-induced damage. Using fluorescence microscopy and electrophysiology, we demonstrated that the natural compounds confer protection by reducing antibiotic uptake into hair cells and showed that hair cells remain functional during and after incubation in E6 berbamine. We also determined that these natural compounds do not reduce antibiotic efficacy. Together, these natural compounds represent a novel source of possible otoprotective drugs that may offer therapeutic options for patients receiving aminoglycoside treatment.

  8. Natural Bizbenzoquinoline Derivatives Protect Zebrafish Lateral Line Sensory Hair Cells from Aminoglycoside Toxicity

    PubMed Central

    Kruger, Matthew; Boney, Robert; Ordoobadi, Alexander J.; Sommers, Thomas F.; Trapani, Josef G.; Coffin, Allison B.

    2016-01-01

    Moderate to severe hearing loss affects 360 million people worldwide and most often results from damage to sensory hair cells. Hair cell damage can result from aging, genetic mutations, excess noise exposure, and certain medications including aminoglycoside antibiotics. Aminoglycosides are effective at treating infections associated with cystic fibrosis and other life-threatening conditions such as sepsis, but cause hearing loss in 20–30% of patients. It is therefore imperative to develop new therapies to combat hearing loss and allow safe use of these potent antibiotics. We approach this drug discovery question using the larval zebrafish lateral line because zebrafish hair cells are structurally and functionally similar to mammalian inner ear hair cells and respond similarly to toxins. We screened a library of 502 natural compounds in order to identify novel hair cell protectants. Our screen identified four bisbenzylisoquinoline derivatives: berbamine, E6 berbamine, hernandezine, and isotetrandrine, each of which robustly protected hair cells from aminoglycoside-induced damage. Using fluorescence microscopy and electrophysiology, we demonstrated that the natural compounds confer protection by reducing antibiotic uptake into hair cells and showed that hair cells remain functional during and after incubation in E6 berbamine. We also determined that these natural compounds do not reduce antibiotic efficacy. Together, these natural compounds represent a novel source of possible otoprotective drugs that may offer therapeutic options for patients receiving aminoglycoside treatment. PMID:27065807

  9. Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome.

    PubMed

    Hurd, Elizabeth A; Adams, Meredith E; Layman, Wanda S; Swiderski, Donald L; Beyer, Lisa A; Halsey, Karin E; Benson, Jennifer M; Gong, Tzy-Wen; Dolan, David F; Raphael, Yehoash; Martin, Donna M

    2011-12-01

    Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression in mature middle and inner ears, analyzed morphological features of mutant ears and tested whether Chd7 mutant mice have altered responses to noise exposure and correlated those responses to inner and middle ear structure. We found that Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles. There were no obvious defects in individual hair cell morphology by prestin immunostaining or scanning electron microscopy, and cochlear innervation appeared normal in Chd7(Gt)(/+) mice. Hearing thresholds by auditory brainstem response (ABR) testing were elevated at 4 and 16 kHz in Chd7(Gt)(/+) mice, and there were reduced distortion product otoacoustic emissions (DPOAE). Exposure of Chd7(Gt)(/+) mice to broadband noise resulted in variable degrees of hair cell loss which inversely correlated with severity of stapedial defects. The degrees of hair cell loss and threshold shifts after noise exposure were more severe in wild type mice than in mutants. Together, these data indicate that Chd7(Gt)(/+) mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Making connections in the inner ear: recent insights into the development of spiral ganglion neurons and their connectivity with sensory hair cells

    PubMed Central

    Coate, Thomas M.; Kelley, Matthew W.

    2013-01-01

    In mammals, auditory information is processed by the hair cells (HCs) located in the cochlea and then rapidly transmitted to the CNS via a specialized cluster of bipolar afferent connections known as the spiral ganglion neurons (SGNs). Although many anatomical aspects of SGNs are well described, the molecular and cellular mechanisms underlying their genesis, how they are precisely arranged along the cochlear duct, and the guidance mechanisms that promote the innervation of their hair cell targets are only now being understood. Building upon foundational studies of neurogenesis and neurotrophins, we review here new concepts and technologies that are helping to enrich our understanding of the development of the nervous system within the inner ear. PMID:23660234

  11. How minute sooglossid frogs hear without a middle ear.

    PubMed

    Boistel, Renaud; Aubin, Thierry; Cloetens, Peter; Peyrin, Françoise; Scotti, Thierry; Herzog, Philippe; Gerlach, Justin; Pollet, Nicolas; Aubry, Jean-François

    2013-09-17

    Acoustic communication is widespread in animals. According to the sensory drive hypothesis [Endler JA (1993) Philos Trans R Soc Lond B Biol Sci 340(1292):215-225], communication signals and perceptual systems have coevolved. A clear illustration of this is the evolution of the tetrapod middle ear, adapted to life on land. Here we report the discovery of a bone conduction-mediated stimulation of the ear by wave propagation in Sechellophryne gardineri, one of the world's smallest terrestrial tetrapods, which lacks a middle ear yet produces acoustic signals. Based on X-ray synchrotron holotomography, we measured the biomechanical properties of the otic tissues and modeled the acoustic propagation. Our models show how bone conduction enhanced by the resonating role of the mouth allows these seemingly deaf frogs to communicate effectively without a middle ear.

  12. Isolation and characterization of the progenitor cells from the blastema tissue formed at experimentally-created rabbit ear hole.

    PubMed

    Baghaban Eslaminejad, Mohamadreza; Bordbar, Sima

    2013-02-01

    Objective(s) : Throughout evolution, mammalians have increasingly lost their ability to regenerate structures however rabbits are exceptional since they develop a blastema in their ear wound for regeneration purposes. Blastema consists of a group of undifferentiated cells capable of dividing and differentiating into the ear tissue. The objective of the present study is to isolate, culture expand, and characterize blastema progenitor cells in terms of their in vitro differentiation capacity. Five New Zealand white male rabbits were used in the present study. Using a punching apparatus, a 4-mm hole was created in the animal ears. Following 4 days, the blastema ring which was created in the periphery of primary hole in the ears was removed and cultivated. The cells migrated from the blastema were expanded through 3 successive subcultures and characterized in terms of their potential differentiation, growth characteristics, and culture requirements. The primary cultures tended to be morphologically heterogeneous having spindly-shaped fibroblast-like cells as well as flattened cells. Fibroblast-like cells survived and dominated the cultures. These cells tended to have the osteogenic, chondrogenic, and adipogenic differentiation potentials. They were highly colonogenic and maximum proliferation was achieved when the cells were plated at density of 100 cells/cm2 in a medium which contained 10% fetal bovine serum (FBS). Taken together, blastema tissue-derived stem cells from rabbit ear are of mesenchymal stem cell-like population. Studies similar to this will assist scientist better understanding the nature of blastema tissue formed at rabbit ear to regenerate the wound.

  13. BODIPY-Conjugated Xyloside Primes Fluorescent Glycosaminoglycans in the Inner Ear of Opsanus tau.

    PubMed

    Holman, Holly A; Tran, Vy M; Kalita, Mausam; Nguyen, Lynn N; Arungundram, Sailaja; Kuberan, Balagurunathan; Rabbitt, Richard D

    2016-12-01

    We report on a new xyloside conjugated to BODIPY, BX and its utility to prime fluorescent glycosaminoglycans (BX-GAGs) within the inner ear in vivo. When BX is administered directly into the endolymphatic space of the oyster toadfish (Opsanus tau) inner ear, fluorescent BX-GAGs are primed and become visible in the sensory epithelia of the semicircular canals, utricle, and saccule. Confocal and 2-photon microscopy of vestibular organs fixed 4 h following BX treatment, reveal BX-GAGs constituting glycocalyces that envelop hair cell kinocilium, nerve fibers, and capillaries. In the presence of GAG-specific enzymes, the BX-GAG signals are diminished, suggesting that chondroitin sulfates are the primary GAGs primed by BX. Results are consistent with similar click-xylosides in CHO cell lines, where the xyloside enters the Golgi and preferentially initiates chondroitin sulfate B production. Introduction of BX produces a temporary block of hair cell mechanoelectrical transduction (MET) currents in the crista, reduction in background discharge rate of afferent neurons, and a reduction in sensitivity to physiological stimulation. A six-degree-of-freedom pharmacokinetic mathematical model has been applied to interpret the time course and spatial distribution of BX and BX-GAGs. Results demonstrate a new optical approach to study GAG biology in the inner ear, for tracking synthesis and localization in real time.

  14. Functional recovery in the avian ear after hair cell regeneration.

    PubMed

    Smolders, J W

    1999-01-01

    Trauma to the inner ear in birds, due to acoustic overstimulation or ototoxic aminoglycosides, can lead to hair cell loss which is followed by regeneration of new hair cells. These processes are paralleled by hearing loss followed by significant functional recovery. After acoustic trauma, functional recovery is rapid and nearly complete. The early and major part of functional recovery after sound trauma occurs before regenerated hair cells become functional. Even very intense sound trauma causes loss of only a proportion of the hair cell population, mainly so-called short hair cells residing on the abneural mobile part of the avian basilar membrane. Uncoupling of the tectorial membrane from the hair cells during sound overexposure may serve as a protection mechanism. The rapid functional recovery after sound trauma appears not to be associated with regeneration of the lost hair cells, but with repair processes involving the surviving hair cells. Small residual functional deficits after recovery are most likely associated with the missing upper fibrous layer of the tectorial membrane which fails to regenerate after sound trauma. After aminoglycoside trauma, functional recovery is slower and parallels the structural regeneration more closely. Aminoglycosides cause damage to both types of hair cells, starting at the basal (high frequency) part of the basilar papilla. However, functional hearing loss and recovery also occur at lower frequencies, associated with areas of the papilla where hair cells survive. Functional recovery in these low frequency areas is complete, whereas functional recovery in high frequency areas with complete hair cell loss is incomplete, despite regeneration of the hair cells. Permanent residual functional deficits remain. This indicates that in low frequency regions functional recovery after aminoglycosides involves repair of nonlethal injury to hair cells and/or hair cell-neural synapses. In the high frequency regions functional recovery

  15. Intrinsic regenerative potential of murine cochlear supporting cells.

    PubMed

    Sinkkonen, Saku T; Chai, Renjie; Jan, Taha A; Hartman, Byron H; Laske, Roman D; Gahlen, Felix; Sinkkonen, Wera; Cheng, Alan G; Oshima, Kazuo; Heller, Stefan

    2011-01-01

    The lack of cochlear regenerative potential is the main cause for the permanence of hearing loss. Albeit quiescent in vivo, dissociated non-sensory cells from the neonatal cochlea proliferate and show ability to generate hair cell-like cells in vitro. Only a few non-sensory cell-derived colonies, however, give rise to hair cell-like cells, suggesting that sensory progenitor cells are a subpopulation of proliferating non-sensory cells. Here we purify from the neonatal mouse cochlea four different non-sensory cell populations by fluorescence-activated cell sorting (FACS). All four populations displayed proliferative potential, but only lesser epithelial ridge and supporting cells robustly gave rise to hair cell marker-positive cells. These results suggest that cochlear supporting cells and cells of the lesser epithelial ridge show robust potential to de-differentiate into prosensory cells that proliferate and undergo differentiation in similar fashion to native prosensory cells of the developing inner ear.

  16. Calcium oxalate stone formation in the inner ear as a result of an Slc26a4 mutation.

    PubMed

    Dror, Amiel A; Politi, Yael; Shahin, Hashem; Lenz, Danielle R; Dossena, Silvia; Nofziger, Charity; Fuchs, Helmut; Hrabé de Angelis, Martin; Paulmichl, Markus; Weiner, Steve; Avraham, Karen B

    2010-07-09

    Calcium oxalate stone formation occurs under pathological conditions and accounts for more than 80% of all types of kidney stones. In the current study, we show for the first time that calcium oxalate stones are formed in the mouse inner ear of a genetic model for hearing loss and vestibular dysfunction in humans. The vestibular system within the inner ear is dependent on extracellular tiny calcium carbonate minerals for proper function. Thousands of these biominerals, known as otoconia, are associated with the utricle and saccule sensory maculae and are vital for mechanical stimulation of the sensory hair cells. We show that a missense mutation within the Slc26a4 gene abolishes the transport activity of its encoded protein, pendrin. As a consequence, dramatic changes in mineral composition, size, and shape occur within the utricle and saccule in a differential manner. Although abnormal giant carbonate minerals reside in the utricle at all ages, in the saccule, a gradual change in mineral composition leads to a formation of calcium oxalate in adult mice. By combining imaging and spectroscopy tools, we determined the profile of mineral composition and morphology at different time points. We propose a novel mechanism for the accumulation and aggregation of oxalate crystals in the inner ear.

  17. Sensory Flask Cells in Sponge Larvae Regulate Metamorphosis via Calcium Signaling.

    PubMed

    Nakanishi, Nagayasu; Stoupin, Daniel; Degnan, Sandie M; Degnan, Bernard M

    2015-12-01

    The Porifera (sponges) is one of the earliest phyletic lineages to branch off the metazoan tree. Although the body-plan of sponges is among the simplest in the animal kingdom and sponges lack nervous systems that communicate environmental signals to other cells, their larvae have sensory systems that generate coordinated responses to environmental cues. In eumetazoans (Cnidaria and Bilateria), the nervous systems of larvae often regulate metamorphosis through Ca(2+)-dependent signal transduction. In sponges, neither the identity of the receptor system that detects an inductive environmental cue (hereafter "metamorphic cues") nor the signaling system that mediates settlement and metamorphosis are known. Using a combination of behavioral assays and surgical manipulations, we show here that specialized epithelial cells-referred to as flask cells-enriched in the anterior third of the Amphimedon queenslandica larva are most likely to be the sensory cells that detect the metamorphic cues. Surgical removal of the region enriched in flask cells in a larva inhibits the initiation of metamorphosis. The flask cell has an apical sensory apparatus with a cilium surrounded by an apical F-actin-rich protrusion, and numerous vesicles, hallmarks of eumetazoan sensory-neurosecretory cells. We demonstrate that these flask cells respond to metamorphic cues by elevating intracellular Ca(2+) levels, and that this elevation is necessary for the initiation of metamorphosis. Taken together, these analyses suggest that sponge larvae have sensory-secretory epithelial cells capable of converting exogenous cues into internal signals via Ca(2+)-mediated signaling, which is necessary for the initiation of metamorphosis. Similarities in the morphology, physiology, and function of the sensory flask cells in sponge larvae with the sensory/neurosecretory cells in eumetazoan larvae suggest this sensory system predates the divergence of Porifera and Eumetazoa. © The Author 2015. Published by Oxford

  18. Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

    PubMed Central

    Sekerková, Gabriella; Zheng, Lili; Loomis, Patricia A.; Mugnaini, Enrico; Bartles, James R.

    2008-01-01

    The espins are novel actin-bundling proteins that are produced in multiple isoforms from a single gene. They are present at high concentration in the parallel actin bundle of hair cell stereocilia and are the target of deafness mutations in mice and humans. Espins are also enriched in the microvilli of taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells, suggesting that espins play important roles in the microvillar projections of vertebrate sensory cells. Espins are potent actin-bundling proteins that are not inhibited by Ca2+. In cells, they efficiently elongate parallel actin bundles and, thereby, help determine the steady-state length of microvilli and stereocilia. Espins bind actin monomer via their WH2 domain and can assemble actin bundles in cells. Certain espin isoforms can also bind phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. These biological activities distinguish espins from other actin-bundling proteins and may make them well-suited to sensory cells. PMID:16909209

  19. Retinoic Acid Signaling Mediates Hair Cell Regeneration by Repressing p27kip and sox2 in Supporting Cells.

    PubMed

    Rubbini, Davide; Robert-Moreno, Àlex; Hoijman, Esteban; Alsina, Berta

    2015-11-25

    During development, otic sensory progenitors give rise to hair cells and supporting cells. In mammalian adults, differentiated and quiescent sensory cells are unable to generate new hair cells when these are lost due to various insults, leading to irreversible hearing loss. Retinoic acid (RA) has strong regenerative capacity in several organs, but its role in hair cell regeneration is unknown. Here, we use genetic and pharmacological inhibition to show that the RA pathway is required for hair cell regeneration in zebrafish. When regeneration is induced by laser ablation in the inner ear or by neomycin treatment in the lateral line, we observe rapid activation of several components of the RA pathway, with dynamics that position RA signaling upstream of other signaling pathways. We demonstrate that blockade of the RA pathway impairs cell proliferation of supporting cells in the inner ear and lateral line. Moreover, in neuromast, RA pathway regulates the transcription of p27(kip) and sox2 in supporting cells but not fgf3. Finally, genetic cell-lineage tracing using Kaede photoconversion demonstrates that de novo hair cells derive from FGF-active supporting cells. Our findings reveal that RA has a pivotal role in zebrafish hair cell regeneration by inducing supporting cell proliferation, and shed light on the underlying transcriptional mechanisms involved. This signaling pathway might be a promising approach for hearing recovery. Hair cells are the specialized mechanosensory cells of the inner ear that capture auditory and balance sensory input. Hair cells die after acoustic trauma, ototoxic drugs or aging diseases, leading to progressive hearing loss. Mammals, in contrast to zebrafish, lack the ability to regenerate hair cells. Here, we find that retinoic acid (RA) pathway is required for hair cell regeneration in vivo in the zebrafish inner ear and lateral line. RA pathway is activated very early upon hair cell loss, promotes cell proliferation of progenitor cells

  20. Understanding the evolution and development of neurosensory transcription factors of the ear to enhance therapeutic translation

    PubMed Central

    Pan, Ning; Kopecky, Benjamin; Jahan, Israt; Fritzsch, Bernd

    2012-01-01

    Reconstructing a functional organ of Corti is the ultimate target towards curing hearing loss. Despite the impressive technical gains made over the last few years, many complications remain ahead for the two main restoration avenues: in vitro transformation of pluripotent cells into hair cell-like cells and adenovirus-mediated gene therapy. Most notably, both approaches require a more complete understanding of the molecular networks that ensure specific cell types form in the correct places to allow proper function of the restored organ of Corti. Important to this understanding are the basic helix-loop-helix (bHLH) transcription factors (TFs) that are highly diverse and serve to increase functional complexity but their evolutionary implementation in the inner ear neurosensory development is less conspicuous. To this end, we review the evolutionary and developmentally dynamic interactions of the three bHLH TFs that have been identified as the main players in neurosensory evolution and development, Neurog1, Neurod1 and Atoh1. These three TFs belong to the neurogenin/atonal family and evolved from a molecular precursor that likely regulated single sensory cell development in the ectoderm of metazoan ancestors but are now also expressed in other parts of the body, including the brain. They interact extensively via intracellular and intercellular cross-regulation to establish the two main neurosensory cell types of the ear, the hair cells and sensory neurons. Furthermore, the level and duration of their expression affect the specification of hair cell subtypes (inner hair cells vs. outer hair cells). We propose that appropriate manipulation of these TFs through their characterized binding sites may offer a solution by itself, or in conjunction with the two other approaches currently pursued by others, to restore the organ of Corti. PMID:22688958

  1. Piezo- and Flexoelectric Membrane Materials Underlie Fast Biological Motors in the Ear

    PubMed Central

    Breneman, Kathryn D.; Rabbitt, Richard D.

    2010-01-01

    The mammalian inner ear is remarkably sensitive to quiet sounds, exhibits over 100dB dynamic range, and has the exquisite ability to discriminate closely spaced tones even in the presence of noise. This performance is achieved, in part, through active mechanical amplification of vibrations by sensory hair cells within the inner ear. All hair cells are endowed with a bundle of motile microvilli, stereocilia, located at the apical end of the cell, and the more specialized outer hair cells (OHC’s) are also endowed with somatic electromotility responsible for changes in cell length in response to perturbations in membrane potential. Both hair bundle and somatic motors are known to feed energy into the mechanical vibrations in the inner ear. The biophysical origin and relative significance of the motors remains a subject of intense research. Several biological motors have been identified in hair cells that might underlie the motor(s), including a cousin of the classical ATP driven actin-myosin motor found in skeletal muscle. Hydrolysis of ATP, however, is much too slow to be viable at audio frequencies on a cycle-by-cycle basis. Heuristically, the OHC somatic motor behaves as if the OHC lateral wall membrane were a piezoelectric material and the hair bundle motor behaves as if the plasma membrane were a flexoelectric material. We propose these observations from a continuum materials perspective are literally true. To examine this idea, we formulated mathematical models of the OHC lateral wall “piezoelectric” motor and the more ubiquitous “flexoelectric” hair bundle motor. Plausible biophysical mechanisms underlying piezo- and flexoelectricity were established. Model predictions were compared extensively to the available data. The models were then applied to study the power conversion efficiency of the motors. Results show that the material properties of the complex membranes in hair cells provide them with the ability to convert electrical power available in

  2. [Investigation of neural stem cell-derived donor contribution in the inner ear following blastocyst injection].

    PubMed

    Volkenstein, S; Brors, D; Hansen, S; Mlynski, R; Dinger, T C; Müller, A M; Dazert, S

    2008-03-01

    Utilising the enormous proliferation and multi-lineage differentiation potentials of somatic stem cells represents a possible therapeutical strategy for diseases of non-regenerative tissues like the inner ear. In the current study, the possibility of murine neural stem cells to contribute to the developing inner ear following blastocyst injection was investigated. Fetal brain-derived neural stem cells from the embryonic day 14 cortex of male mice were isolated and expanded for four weeks in neurobasal media supplemented with bFGF and EGF. Neural stem cells of male animals were harvested, injected into blastocysts and the blastocysts were transferred into pseudo-pregnant foster animals. Each blastocyst was injected with 5-15 microspheres growing from single cell suspension from neurospheres dissociated the day before. The resulting mice were investigated six months POST PARTUM for the presence of donor cells. Brainstem evoked response audiometry (BERA) was performed in six animals. To visualize donor cells Lac-Z staining was performed on sliced cochleas of two animals. In addition, the cochleas of four female animals were isolated and genomic DNA of the entire cochlea was analyzed for donor contribution by Y-chromosome-specific PCR. All animals had normal thresholds in brainstem evoked response audiometry. The male-specific PCR product indicating the presence of male donor cells were detected in the cochleas of three of the four female animals investigated. In two animals, male donor cells were detected unilateral, in one animal bilateral. The results suggest that descendants of neural stem cells are detectable in the inner ear after injection into blastocysts and possess the ability to integrate into the developing inner ear without obvious loss in hearing function.

  3. The genetics of hair-cell function in zebrafish.

    PubMed

    Nicolson, Teresa

    2017-09-01

    Our ears are remarkable sensory organs, providing the important senses of balance and hearing. The complex structure of the inner ear, or 'labyrinth', along with the assorted neuroepithelia, have evolved to detect head movements and sounds with impressive sensitivity. The rub is that the inner ear is highly vulnerable to genetic lesions and environmental insults. According to National Institute of Health estimates, hearing loss is one of the most commonly inherited or acquired sensorineural diseases. To understand the causes of deafness and balance disorders, it is imperative to understand the underlying biology of the inner ear, especially the inner workings of the sensory receptors. These receptors, which are termed hair cells, are particularly susceptible to genetic mutations - more than two dozen genes are associated with defects in this cell type in humans. Over the past decade, a substantial amount of progress has been made in working out the molecular basis of hair-cell function using vertebrate animal models. Given the transparency of the inner ear and the genetic tools that are available, zebrafish have become an increasingly popular animal model for the study of deafness and vestibular dysfunction. Mutagenesis screens for larval defects in hearing and balance have been fruitful in finding key components, many of which have been implicated in human deafness. This review will focus on the genes that are required for hair-cell function in zebrafish, with a particular emphasis on mechanotransduction. In addition, the generation of new tools available for the characterization of zebrafish hair-cell mutants will be discussed.

  4. A central to peripheral progression of cell cycle exit and hair cell differentiation in the developing mouse cristae

    PubMed Central

    Slowik, Amber D; Bermingham-McDonogh, Olivia

    2016-01-01

    The inner ear contains six distinct sensory organs that each maintains some ability to regenerate hair cells into adulthood. In the postnatal cochlea, there appears to be a relationship between the developmental maturity of a region and its ability to regenerate as postnatal regeneration largely occurs in the apical turn, which is the last region to differentiate and mature during development. In the mature cristae there are also regional differences in regenerative ability, which led us to hypothesize that there may be a general relationship between the relative maturity of a region and the regenerative competence of that region in all of the inner ear sensory organs. By analyzing adult mouse cristae labeled embryonically with BrdU, we found that hair cell birth starts in the central region and progresses to the periphery with age. Since the peripheral region of the adult cristae also maintains active Notch signaling and some regenerative competence, these results are consistent with the hypothesis that the last regions to develop retain some of their regenerative ability into adulthood. Further, by analyzing embryonic day 14.5 inner ears we provide evidence for a wave of hair cell birth along the longitudinal axis of the cristae from the central regions to the outer edges. Together with the data from the adult inner ears labeled with BrdU as embryos, these results suggest that hair cell differentiation closely follows cell cycle exit in the cristae, unlike in the cochlea where they are uncoupled. PMID:26826497

  5. Human middle-ear model with compound eardrum and airway branching in mastoid air cells

    PubMed Central

    Keefe, Douglas H.

    2015-01-01

    An acoustical/mechanical model of normal adult human middle-ear function is described for forward and reverse transmission. The eardrum model included one component bound along the manubrium and another bound by the tympanic cleft. Eardrum components were coupled by a time-delayed impedance. The acoustics of the middle-ear cleft was represented by an acoustical transmission-line model for the tympanic cavity, aditus, antrum, and mastoid air cell system with variable amounts of excess viscothermal loss. Model parameters were fitted to published measurements of energy reflectance (0.25–13 kHz), equivalent input impedance at the eardrum (0.25–11 kHz), temporal-bone pressure in scala vestibuli and scala tympani (0.1–11 kHz), and reverse middle-ear impedance (0.25–8 kHz). Inner-ear fluid motion included cochlear and physiological third-window pathways. The two-component eardrum with time delay helped fit intracochlear pressure responses. A multi-modal representation of the eardrum and high-frequency modeling of the middle-ear cleft helped fit ear-canal responses. Input reactance at the eardrum was small at high frequencies due to multiple modal resonances. The model predicted the middle-ear efficiency between ear canal and cochlea, and the cochlear pressures at threshold. PMID:25994701

  6. Human middle-ear model with compound eardrum and airway branching in mastoid air cells.

    PubMed

    Keefe, Douglas H

    2015-05-01

    An acoustical/mechanical model of normal adult human middle-ear function is described for forward and reverse transmission. The eardrum model included one component bound along the manubrium and another bound by the tympanic cleft. Eardrum components were coupled by a time-delayed impedance. The acoustics of the middle-ear cleft was represented by an acoustical transmission-line model for the tympanic cavity, aditus, antrum, and mastoid air cell system with variable amounts of excess viscothermal loss. Model parameters were fitted to published measurements of energy reflectance (0.25-13 kHz), equivalent input impedance at the eardrum (0.25-11 kHz), temporal-bone pressure in scala vestibuli and scala tympani (0.1-11 kHz), and reverse middle-ear impedance (0.25-8 kHz). Inner-ear fluid motion included cochlear and physiological third-window pathways. The two-component eardrum with time delay helped fit intracochlear pressure responses. A multi-modal representation of the eardrum and high-frequency modeling of the middle-ear cleft helped fit ear-canal responses. Input reactance at the eardrum was small at high frequencies due to multiple modal resonances. The model predicted the middle-ear efficiency between ear canal and cochlea, and the cochlear pressures at threshold.

  7. The cytokine macrophage migration inhibitory factor (MIF) acts as a neurotrophin in the developing inner ear of the zebrafish, Danio rerio

    PubMed Central

    Shen, Yu-chi; Thompson, Deborah L.; Kuah, Meng-Kiat; Wong, Kah-Loon; Wu, Karen L.; Linn, Stephanie A.; Jewett, Ethan M.; Shu-Chien, Alexander Chong; Barald, Kate F.

    2012-01-01

    Macrophage migration inhibitory factor (MIF) plays versatile roles in the immune system. MIF is also widely expressed during embryonic development, particularly in the nervous system, although its roles in neural development are only beginning to be understood. Evidence from frogs, mice and zebrafish suggests that MIF has a major role as a neurotrophin in the early development of sensory systems, including the auditory system. Here we show that the zebrafish mif pathway is required for both sensory hair cell (HC) and sensory neuronal cell survival in the ear, for HC differentiation, semicircular canal formation, statoacoustic ganglion (SAG) development, and lateral line HC differentiation. This is consistent with our findings that MIF is expressed in the developing mammalian and avian auditory systems and promotes mouse and chick SAG neurite outgrowth and neuronal survival, demonstrating key instructional roles for MIF in vertebrate otic development. PMID:22210003

  8. Diphtheria Toxin-Induced Cell Death Triggers Wnt-Dependent Hair Cell Regeneration in Neonatal Mice.

    PubMed

    Hu, Lingxiang; Lu, Jingrong; Chiang, Hao; Wu, Hao; Edge, Albert S B; Shi, Fuxin

    2016-09-07

    Cochlear hair cells (HCs), the sensory cells that respond to sound, do not regenerate after damage in adult mammals, and their loss is a major cause of deafness. Here we show that HC regeneration in newborn mouse ears occurred spontaneously when the original cells were ablated by treatment with diphtheria toxin (DT) in ears that had been engineered to overexpress the DT receptor, but was not detectable when HCs were ablated in vivo by the aminoglycoside antibiotic neomycin. A variety of Wnts (Wnt1, Wnt2, Wnt2b, Wnt4, Wnt5a, Wnt7b, Wnt9a, Wnt9b, and Wnt11) and Wnt pathway component Krm2 were upregulated after DT damage. Nuclear β-catenin was upregulated in HCs and supporting cells of the DT-damaged cochlea. Pharmacological inhibition of Wnt decreased spontaneous regeneration, confirming a role of Wnt signaling in HC regeneration. Inhibition of Notch signaling further potentiated supporting cell proliferation and HC differentiation that occurred spontaneously. The absence of new HCs in the neomycin ears was correlated to less robust Wnt pathway activation, but the ears subjected to neomycin treatment nonetheless showed increased cell division and HC differentiation after subsequent forced upregulation of β-catenin. These studies suggest, first, that Wnt signaling plays a key role in regeneration, and, second, that the outcome of a regenerative response to damage in the newborn cochlea is determined by reaching a threshold level of Wnt signaling rather than its complete absence or presence. Sensory HCs of the inner ear do not regenerate in the adult, and their loss is a major cause of deafness. We found that HCs regenerated spontaneously in the newborn mouse after diphtheria toxin (DT)-induced, but not neomycin-induced, HC death. Regeneration depended on activation of Wnt signaling, and regeneration in DT-treated ears correlated to a higher level of Wnt activation than occurred in nonregenerating neomycin-treated ears. This is significant because insufficient

  9. Diphtheria Toxin-Induced Cell Death Triggers Wnt-Dependent Hair Cell Regeneration in Neonatal Mice

    PubMed Central

    Hu, Lingxiang; Lu, Jingrong; Chiang, Hao; Shi, Fuxin

    2016-01-01

    Cochlear hair cells (HCs), the sensory cells that respond to sound, do not regenerate after damage in adult mammals, and their loss is a major cause of deafness. Here we show that HC regeneration in newborn mouse ears occurred spontaneously when the original cells were ablated by treatment with diphtheria toxin (DT) in ears that had been engineered to overexpress the DT receptor, but was not detectable when HCs were ablated in vivo by the aminoglycoside antibiotic neomycin. A variety of Wnts (Wnt1, Wnt2, Wnt2b, Wnt4, Wnt5a, Wnt7b, Wnt9a, Wnt9b, and Wnt11) and Wnt pathway component Krm2 were upregulated after DT damage. Nuclear β-catenin was upregulated in HCs and supporting cells of the DT-damaged cochlea. Pharmacological inhibition of Wnt decreased spontaneous regeneration, confirming a role of Wnt signaling in HC regeneration. Inhibition of Notch signaling further potentiated supporting cell proliferation and HC differentiation that occurred spontaneously. The absence of new HCs in the neomycin ears was correlated to less robust Wnt pathway activation, but the ears subjected to neomycin treatment nonetheless showed increased cell division and HC differentiation after subsequent forced upregulation of β-catenin. These studies suggest, first, that Wnt signaling plays a key role in regeneration, and, second, that the outcome of a regenerative response to damage in the newborn cochlea is determined by reaching a threshold level of Wnt signaling rather than its complete absence or presence. SIGNIFICANCE STATEMENT Sensory HCs of the inner ear do not regenerate in the adult, and their loss is a major cause of deafness. We found that HCs regenerated spontaneously in the newborn mouse after diphtheria toxin (DT)-induced, but not neomycin-induced, HC death. Regeneration depended on activation of Wnt signaling, and regeneration in DT-treated ears correlated to a higher level of Wnt activation than occurred in nonregenerating neomycin-treated ears. This is significant

  10. Modelling effects on grid cells of sensory input during self‐motion

    PubMed Central

    Raudies, Florian; Hinman, James R.

    2016-01-01

    Abstract The neural coding of spatial location for memory function may involve grid cells in the medial entorhinal cortex, but the mechanism of generating the spatial responses of grid cells remains unclear. This review describes some current theories and experimental data concerning the role of sensory input in generating the regular spatial firing patterns of grid cells, and changes in grid cell firing fields with movement of environmental barriers. As described here, the influence of visual features on spatial firing could involve either computations of self‐motion based on optic flow, or computations of absolute position based on the angle and distance of static visual cues. Due to anatomical selectivity of retinotopic processing, the sensory features on the walls of an environment may have a stronger effect on ventral grid cells that have wider spaced firing fields, whereas the sensory features on the ground plane may influence the firing of dorsal grid cells with narrower spacing between firing fields. These sensory influences could contribute to the potential functional role of grid cells in guiding goal‐directed navigation. PMID:27094096

  11. Coenzyme Q10 protects hair cells against aminoglycoside.

    PubMed

    Sugahara, Kazuma; Hirose, Yoshinobu; Mikuriya, Takefumi; Hashimoto, Makoto; Kanagawa, Eiju; Hara, Hirotaka; Shimogori, Hiroaki; Yamashita, Hiroshi

    2014-01-01

    It is well known that the production of free radicals is associated with sensory cell death induced by an aminoglycoside. Many researchers have reported that antioxidant reagents protect sensory cells in the inner ear, and coenzyme Q10 (CoQ10) is an antioxidant that is consumed as a health food in many countries. The purpose of this study was to investigate the role of CoQ10 in mammalian vestibular hair cell death induced by aminoglycoside. Cultured utricles of CBA/CaN mice were divided into three groups (control group, neomycin group, and neomycin + CoQ10 group). In the neomycin group, utricles were cultured with neomycin (1 mM) to induce hair cell death. In the neomycin + CoQ10 group, utricles were cultured with neomycin and water-soluble CoQ10 (30-0.3 µM). Twenty-four hours after exposure to neomycin, the cultured tissues were fixed, and vestibular hair cells were labeled using an anti-calmodulin antibody. Significantly more hair cells survived in the neomycin + CoQ10 group than in the neomycin group. These data indicate that CoQ10 protects sensory hair cells against neomycin-induced death in the mammalian vestibular epithelium; therefore, CoQ10 may be useful as a protective drug in the inner ear.

  12. Zebrafish models of human eye and inner ear diseases.

    PubMed

    Blanco-Sánchez, B; Clément, A; Phillips, J B; Westerfield, M

    2017-01-01

    Eye and inner ear diseases are the most common sensory impairments that greatly impact quality of life. Zebrafish have been intensively employed to understand the fundamental mechanisms underlying eye and inner ear development. The zebrafish visual and vestibulo-acoustic systems are very similar to these in humans, and although not yet mature, they are functional by 5days post-fertilization (dpf). In this chapter, we show how the zebrafish has significantly contributed to the field of biomedical research and how researchers, by establishing disease models and meticulously characterizing their phenotypes, have taken the first steps toward therapies. We review here models for (1) eye diseases, (2) ear diseases, and (3) syndromes affecting eye and/or ear. The use of new genome editing technologies and high-throughput screening systems should increase considerably the speed at which knowledge from zebrafish disease models is acquired, opening avenues for better diagnostics, treatments, and therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Middle Ear Fluid Cytokine and Inflammatory Cell Kinetics in the Chinchilla Otitis Media Model

    PubMed Central

    Sato, Katsuro; Liebeler, Carol L.; Quartey, Moses K.; Le, Chap T.; Giebink, G. Scott

    1999-01-01

    Streptococcus pneumoniae is the most frequent microbe causing middle ear infection. The pathophysiology of pneumococcal otitis media has been characterized by measurement of local inflammatory mediators such as inflammatory cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The role of cytokines in bacterial infection has been elucidated with animal models, and interleukin (IL)-1β, IL-6, and IL-8 and tumor necrosis factor alpha (TNF-α) are recognized as being important local mediators in acute inflammation. We characterized middle ear inflammatory responses in the chinchilla otitis media model after injecting a very small number of viable pneumococci into the middle ear, similar to the natural course of infection. Middle ear fluid (MEF) concentrations of IL-1β, IL-6, IL-8, and TNF-α were measured by using anti-human cytokine enzyme-linked immunosorbent assay reagents. IL-1β showed the earliest peak, at 6 h after inoculation, whereas IL-6, IL-8, and TNF-α concentrations were increasing 72 h after pneumococcal inoculation. IL-6, IL-8, and TNF-α but not IL-1β concentrations correlated significantly with total inflammatory cell numbers in MEF, and all four cytokines correlated significantly with MEF neutrophil concentration. Several intercytokine correlations were significant. Cytokines, therefore, participate in the early middle ear inflammatory response to S. pneumoniae. PMID:10085040

  14. Active middle ear implant after lateral petrosectomy and radiotherapy for ear cancer.

    PubMed

    Cristalli, Giovanni; Sprinzl, Georg M; Wolf-Magele, Astrid; Marchesi, Paolo; Mercante, Giuseppe; Spriano, Giuseppe

    2014-04-01

    Tumor of the temporal bone is a rare disease with a very poor prognosis. Surgery and postoperative radiotherapy are usually the recommended treatments for squamous cell carcinoma (SCC) of the external and middle ear, which may cause conductive hearing loss. The purpose of this study was to evaluate the audiologic results and compliance of active middle ear implant (AMEI) and establish the feasibility of the procedure in a patient treated for middle ear cancer. A 73-year-old patient treated with lateral petrosectomy, neck dissection, reconstruction/obliteration by pedicled pectoralis major myocutaneous flap, and postoperative full dose radiotherapy for external and middle ear SCC was selected for AMEI. Preoperative audiometric and speech audiometry tests were performed on both ears before and after the activation. Pure tone free field audiometry. Binaural free field speech audiogram. Aided pure tone free field audiometry AMEI results show an increase in air conduction. Speech audiogram showed better discrimination scores in AMEI-aided situations. No complications were observed. AMEI after surgery followed by radiotherapy for middle ear cancer is feasible. Acoustic results in obliterated ear are satisfactory.

  15. Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear.

    PubMed

    Kilpatrick, L A; Li, Q; Yang, J; Goddard, J C; Fekete, D M; Lang, H

    2011-06-01

    Murine models are ideal for studying cochlear gene transfer, as many hearing loss-related mutations have been discovered and mapped within the mouse genome. However, because of the small size and delicate nature, the membranous labyrinth of the mouse is a challenging target for the delivery of viral vectors. To minimize injection trauma, we developed a procedure for the controlled release of adeno-associated viruses (AAVs) into the scala media of adult mice. This procedure poses minimal risk of injury to structures of the cochlea and middle ear, and allows for near-complete preservation of low and middle frequency hearing. In this study, transduction efficiency and cellular specificity of AAV vectors (serotypes 1, 2, 5, 6 and 8) were investigated in normal and drug-deafened ears. Using the cytomegalovirus promoter to drive gene expression, a variety of cell types were transduced successfully, including sensory hair cells and supporting cells, as well as cells in the auditory nerve and spiral ligament. Among all five serotypes, inner hair cells were the most effectively transduced cochlear cell type. All five serotypes of AAV vectors transduced cells of the auditory nerve, though serotype 8 was the most efficient vector for transduction. Our findings indicate that efficient AAV inoculation (via the scala media) can be performed in adult mouse ears, with hearing preservation a realistic goal. The procedure we describe may also have applications for intra-endolymphatic drug delivery in many mouse models of human deafness.

  16. Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear

    PubMed Central

    Kilpatrick, Lauren A.; Li, Qian; Yang, John; Goddard, John C; Fekete, Donna M.; Lang, Hainan

    2010-01-01

    Murine models are ideal for studying cochlear gene transfer as many hearing loss-related mutations have been discovered and mapped within the mouse genome. However, due to its small size and delicate nature, the membranous labyrinth of the mouse is a challenging target for delivery of viral vectors. To minimize injection trauma, we developed a procedure for the controlled release of adeno-associated viruses (AAV) into the scala media of adult mice. This procedure poses minimal risk of injury to structures of the cochlea and middle ear and allows for near-complete preservation of low and middle frequency hearing. In the present study, transduction efficiency and cellular specificity of AAV vectors (serotypes 1, 2, 5, 6, and 8) were investigated in normal and drug-deafened ears. Using the cytomegalovirus (CMV) promoter to drive gene expression, a variety of cell types were transduced successfully, including sensory hair cells and supporting cells, as well as cells in the auditory nerve and spiral ligament. Among all five serotypes, inner hair cells (IHCs) were the most effectively transduced cochlear cell type. All five serotypes of AAV vectors transduced cells of the auditory nerve, though serotype 8 was the most efficient vector for transduction. Our findings indicate that efficient AAV inoculation (via the scala media) can be performed in adult mouse ears, with hearing preservation a realistic goal. The procedure we describe may also have applications for intra-endolymphatic drug delivery in many mouse models of human deafness. PMID:21209625

  17. Sensory hair cell development and regeneration: similarities and differences

    PubMed Central

    Atkinson, Patrick J.; Huarcaya Najarro, Elvis; Sayyid, Zahra N.; Cheng, Alan G.

    2015-01-01

    Sensory hair cells are mechanoreceptors of the auditory and vestibular systems and are crucial for hearing and balance. In adult mammals, auditory hair cells are unable to regenerate, and damage to these cells results in permanent hearing loss. By contrast, hair cells in the chick cochlea and the zebrafish lateral line are able to regenerate, prompting studies into the signaling pathways, morphogen gradients and transcription factors that regulate hair cell development and regeneration in various species. Here, we review these findings and discuss how various signaling pathways and factors function to modulate sensory hair cell development and regeneration. By comparing and contrasting development and regeneration, we also highlight the utility and limitations of using defined developmental cues to drive mammalian hair cell regeneration. PMID:25922522

  18. Hair Cell Heterogeneity in the Goldfish Saccule

    NASA Technical Reports Server (NTRS)

    Saidel, William M.; Lanford, Pamela J.; Yan, Hong Y.; Popper, Arthur N.

    1995-01-01

    A set of cytological studies performed in the utricle and saccule of Astronotus ocellatus (Teleostei, Percomorphi, Cichlidae) identified two basic types of hair cells and others with some intermediate characteristics. This paper reports on applying the same techniques to the saccule of Carassius auratus (Teleostei, Otophysi, Cyprinidae) and demonstrates similar types of hair cells to those found in Astronotus. Since Carassius and Astronous are species of extreme taxonomic distance within the Euteteostei, two classes of mechanoreceptive hair cells are likely to represent the primitive condition for sensory receptors in the euteleost inner ear and perhaps in all bony fish ears.

  19. Sensory Transduction and Electrical Signaling in Guard Cells

    PubMed Central

    Serrano, Elba E.; Zeiger, Eduardo

    1989-01-01

    Guard cells are a valuable model system for the study of photoreception, ion transport, and osmoregulation in plant cells. Changes in stomatal apertures occur when sensing mechanisms within the guard cells transduce environmental stimull into the ion fluxes and biosynthesis of organic solutes that regulate turgor. The electrical events mediating sensory transduction in guard cells can be characterized with a variety of electrophysiological recording techniques. Recent experiments applying the patch clamp method to guard cell protoplasts have demonstrated activation of electrogenic pumps by blue and red light as well as the presence of potassium channels in guard cell plasmalemma. Light activation of electrogenic proton pumping and the ensuing gating of voltage-dependent ion channels appear to be components of sensory transduction of the stomatal response to light. Mechanisms underlying stomatal control by environmental signals can be understood by studying electrical events associated with ion transport. PMID:16667138

  20. Scanning Thin-Sheet Laser Imaging Microscopy Elucidates Details on Mouse Ear Development

    PubMed Central

    Kopecky, Benjamin; Johnson, Shane; Schmitz, Heather; Santi, Peter; Fritzsch, Bernd

    2016-01-01

    Background The mammalian inner ear is transformed from a flat placode into a three-dimensional (3D) structure with six sensory epithelia that allow for the perception of sound and both linear and angular acceleration. While hearing and balance problems are typically considered to be adult onset diseases, they may arise as a developmental perturbation to the developing ear. Future prevention of hearing or balance loss requires an understanding of how closely genetic mutations in model organisms reflect the human case, necessitating an objective multidimensional comparison of mouse ears with human ears that have comparable mutations in the same gene. Results Here, we present improved 3D analyses of normal murine ears during embryonic development using optical sections obtained through Thin-Sheet Laser Imaging Microscopy. We chronicle the transformation of an undifferentiated otic vesicle between mouse embryonic day 11.5 to a fully differentiated inner ear at postnatal day 15. Conclusions Our analysis of ear development provides new insights into ear development, enables unique perspectives into the complex development of the ear, and allows for the first full quantification of volumetric and linear aspects of ear growth. Our data provide the framework for future analysis of mutant phenotypes that are currently under-appreciated using only two dimensional renderings. PMID:22271591

  1. Scanning thin-sheet laser imaging microscopy elucidates details on mouse ear development.

    PubMed

    Kopecky, Benjamin; Johnson, Shane; Schmitz, Heather; Santi, Peter; Fritzsch, Bernd

    2012-03-01

    The mammalian inner ear is transformed from a flat placode into a three-dimensional (3D) structure with six sensory epithelia that allow for the perception of sound and both linear and angular acceleration. While hearing and balance problems are typically considered to be adult onset diseases, they may arise as a developmental perturbation to the developing ear. Future prevention of hearing or balance loss requires an understanding of how closely genetic mutations in model organisms reflect the human case, necessitating an objective multidimensional comparison of mouse ears with human ears that have comparable mutations in the same gene. Here, we present improved 3D analyses of normal murine ears during embryonic development using optical sections obtained through Thin-Sheet Laser Imaging Microscopy. We chronicle the transformation of an undifferentiated otic vesicle between mouse embryonic day 11.5 to a fully differentiated inner ear at postnatal day 15. Our analysis of ear development provides new insights into ear development, enables unique perspectives into the complex development of the ear, and allows for the first full quantification of volumetric and linear aspects of ear growth. Our data provide the framework for future analysis of mutant phenotypes that are currently under-appreciated using only two dimensional renderings. Copyright © 2012 Wiley Periodicals, Inc.

  2. A central to peripheral progression of cell cycle exit and hair cell differentiation in the developing mouse cristae.

    PubMed

    Slowik, Amber D; Bermingham-McDonogh, Olivia

    2016-03-01

    The inner ear contains six distinct sensory organs that each maintains some ability to regenerate hair cells into adulthood. In the postnatal cochlea, there appears to be a relationship between the developmental maturity of a region and its ability to regenerate as postnatal regeneration largely occurs in the apical turn, which is the last region to differentiate and mature during development. In the mature cristae there are also regional differences in regenerative ability, which led us to hypothesize that there may be a general relationship between the relative maturity of a region and the regenerative competence of that region in all of the inner ear sensory organs. By analyzing adult mouse cristae labeled embryonically with BrdU, we found that hair cell birth starts in the central region and progresses to the periphery with age. Since the peripheral region of the adult cristae also maintains active Notch signaling and some regenerative competence, these results are consistent with the hypothesis that the last regions to develop retain some of their regenerative ability into adulthood. Further, by analyzing embryonic day 14.5 inner ears we provide evidence for a wave of hair cell birth along the longitudinal axis of the cristae from the central regions to the outer edges. Together with the data from the adult inner ears labeled with BrdU as embryos, these results suggest that hair cell differentiation closely follows cell cycle exit in the cristae, unlike in the cochlea where they are uncoupled. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Three-Dimensional Cell Printing of Large-Volume Tissues: Application to Ear Regeneration.

    PubMed

    Lee, Jung-Seob; Kim, Byoung Soo; Seo, Donghwan; Park, Jeong Hun; Cho, Dong-Woo

    2017-03-01

    The three-dimensional (3D) printing of large-volume cells, printed in a clinically relevant size, is one of the most important challenges in the field of tissue engineering. However, few studies have reported the fabrication of large-volume cell-printed constructs (LCCs). To create LCCs, appropriate fabrication conditions should be established: Factors involved include fabrication time, residence time, and temperature control of the cell-laden hydrogel in the syringe to ensure high cell viability and functionality. The prolonged time required for 3D printing of LCCs can reduce cell viability and result in insufficient functionality of the construct, because the cells are exposed to a harsh environment during the printing process. In this regard, we present an advanced 3D cell-printing system composed of a clean air workstation, a humidifier, and a Peltier system, which provides a suitable printing environment for the production of LCCs with high cell viability. We confirmed that the advanced 3D cell-printing system was capable of providing enhanced printability of hydrogels and fabricating an ear-shaped LCC with high cell viability. In vivo results for the ear-shaped LCC also showed that printed chondrocytes proliferated sufficiently and differentiated into cartilage tissue. Thus, we conclude that the advanced 3D cell-printing system is a versatile tool to create cell-printed constructs for the generation of large-volume tissues.

  4. Integrated annotation and analysis of in situ hybridization images using the ImAnno system: application to the ear and sensory organs of the fetal mouse.

    PubMed

    Romand, Raymond; Ripp, Raymond; Poidevin, Laetitia; Boeglin, Marcel; Geffers, Lars; Dollé, Pascal; Poch, Olivier

    2015-01-01

    An in situ hybridization (ISH) study was performed on 2000 murine genes representing around 10% of the protein-coding genes present in the mouse genome using data generated by the EURExpress consortium. This study was carried out in 25 tissues of late gestation embryos (E14.5), with a special emphasis on the developing ear and on five distinct developing sensory organs, including the cochlea, the vestibular receptors, the sensory retina, the olfactory organ, and the vibrissae follicles. The results obtained from an analysis of more than 11,000 micrographs have been integrated in a newly developed knowledgebase, called ImAnno. In addition to managing the multilevel micrograph annotations performed by human experts, ImAnno provides public access to various integrated databases and tools. Thus, it facilitates the analysis of complex ISH gene expression patterns, as well as functional annotation and interaction of gene sets. It also provides direct links to human pathways and diseases. Hierarchical clustering of expression patterns in the 25 tissues revealed three main branches corresponding to tissues with common functions and/or embryonic origins. To illustrate the integrative power of ImAnno, we explored the expression, function and disease traits of the sensory epithelia of the five presumptive sensory organs. The study identified 623 genes (out of 2000) concomitantly expressed in the five embryonic epithelia, among which many (∼12%) were involved in human disorders. Finally, various multilevel interaction networks were characterized, highlighting differential functional enrichments of directly or indirectly interacting genes. These analyses exemplify an under-represention of "sensory" functions in the sensory gene set suggests that E14.5 is a pivotal stage between the developmental stage and the functional phase that will be fully reached only after birth.

  5. Identification of a role for the nuclear receptor EAR-2 in the maintenance of clonogenic status within the leukemia cell hierarchy

    PubMed Central

    Ichim, CV; Atkins, HL; Iscove, NN; Wells, RA

    2016-01-01

    Identification of genes that regulate clonogenicity of acute myelogenous leukemia (AML) cells is hindered by the difficulty of isolating pure populations of cells with defined proliferative abilities. By analyzing the growth of clonal siblings in low passage cultures of the cell line OCI/AML4 we resolved this heterogeneous population into strata of distinct clonogenic potential, permitting analysis of the transcriptional signature of single cells with defined proliferative abilities. By microarray analysis we showed that the expression of the orphan nuclear receptor EAR-2 (NR2F6) is greater in leukemia cells with extensive proliferative capacity than in those that have lost proliferative ability. EAR-2 is expressed highly in long-term hematopoietic stem cells, relative to short-term hematopoietic stem and progenitor cells, and is downregulated in AML cells after induction of differentiation. Exogenous expression of EAR-2 increased the growth of U937 cells and prevented the proliferative arrest associated with terminal differentiation, and blocked differentiation of U937 and 32Dcl3 cells. Conversely, silencing of EAR-2 by short-hairpin RNA initiated terminal differentiation of these cell lines. These data identify EAR-2 as an important factor in the regulation of clonogenicity and differentiation, and establish that analysis of clonal siblings allows the elucidation of differences in gene expression within the AML hierarchy. PMID:21637284

  6. Better late than never: effective air-borne hearing of toads delayed by late maturation of the tympanic middle ear structures.

    PubMed

    Womack, Molly C; Christensen-Dalsgaard, Jakob; Hoke, Kim L

    2016-10-15

    Most vertebrates have evolved a tympanic middle ear that enables effective hearing of airborne sound on land. Although inner ears develop during the tadpole stages of toads, tympanic middle ear structures are not complete until months after metamorphosis, potentially limiting the sensitivity of post-metamorphic juveniles to sounds in their environment. We tested the hearing of five species of toads to determine how delayed ear development impairs airborne auditory sensitivity. We performed auditory brainstem recordings to test the hearing of the toads and used micro-computed tomography and histology to relate the development of ear structures to hearing ability. We found a large (14-27 dB) increase in hearing sensitivity from 900 to 2500 Hz over the course of ear development. Thickening of the tympanic annulus cartilage and full ossification of the middle ear bone are associated with increased hearing ability in the final stages of ear maturation. Thus, juvenile toads are at a hearing disadvantage, at least in the high-frequency range, throughout much of their development, because late-forming ear elements are critical to middle ear function at these frequencies. We discuss the potential fitness consequences of late hearing development, although research directly addressing selective pressures on hearing sensitivity across ontogeny is lacking. Given that most vertebrate sensory systems function very early in life, toad tympanic hearing may be a sensory development anomaly. © 2016. Published by The Company of Biologists Ltd.

  7. 3D Printed Bionic Ears

    PubMed Central

    Mannoor, Manu S.; Jiang, Ziwen; James, Teena; Kong, Yong Lin; Malatesta, Karen A.; Soboyejo, Winston O.; Verma, Naveen; Gracias, David H.; McAlpine, Michael C.

    2013-01-01

    The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts. Conventional electronic devices are inherently two-dimensional, preventing seamless multidimensional integration with synthetic biology, as the processes and materials are very different. Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements. As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the precise anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing. PMID:23635097

  8. 3D printed bionic ears.

    PubMed

    Mannoor, Manu S; Jiang, Ziwen; James, Teena; Kong, Yong Lin; Malatesta, Karen A; Soboyejo, Winston O; Verma, Naveen; Gracias, David H; McAlpine, Michael C

    2013-06-12

    The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts. Conventional electronic devices are inherently two-dimensional, preventing seamless multidimensional integration with synthetic biology, as the processes and materials are very different. Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements. As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing.

  9. Electrotactile and vibrotactile displays for sensory substitution systems

    NASA Technical Reports Server (NTRS)

    Kaczmarek, Kurt A.; Webster, John G.; Bach-Y-rita, Paul; Tompkins, Willis J.

    1991-01-01

    Sensory substitution systems provide their users with environmental information through a human sensory channel (eye, ear, or skin) different from that normally used or with the information processed in some useful way. The authors review the methods used to present visual, auditory, and modified tactile information to the skin and discuss present and potential future applications of sensory substitution, including tactile vision substitution (TVS), tactile auditory substitution, and remote tactile sensing or feedback (teletouch). The relevant sensory physiology of the skin, including the mechanisms of normal touch and the mechanisms and sensations associated with electrical stimulation of the skin using surface electrodes (electrotactile, or electrocutaneous, stimulation), is reviewed. The information-processing ability of the tactile sense and its relevance to sensory substitution is briefly summarized. The limitations of current tactile display technologies are discussed.

  10. Dynamic activation of basilar membrane macrophages in response to chronic sensory cell degeneration in aging mouse cochleae

    PubMed Central

    Frye, Mitchell D.; Yang, Weiping; Zhang, Celia; Xiong, Binbin; Hu, Bo Hua

    2016-01-01

    In the sensory epithelium, macrophages have been identified on the scala tympani side of the basilar membrane. These basilar membrane macrophages are the spatially closest immune cells to sensory cells and are able to directly respond to and influence sensory cell pathogenesis. While basilar membrane macrophages have been studied in acute cochlear stresses, their behavior in response to chronic sensory cell degeneration is largely unknown. Here we report a systematic observation of the variance in phenotypes, the changes in morphology and distribution of basilar membrane tissue macrophages in different age groups of C57BL/6J mice, a mouse model of age-related sensory cell degeneration. This study reveals that mature, fully differentiated tissue macrophages, not recently infiltrated monocytes, are the major macrophage population for immune responses to chronic sensory cell death. These macrophages display dynamic changes in their numbers and morphologies as age increases, and the changes are related to the phases of sensory cell degeneration. Notably, macrophage activation precedes sensory cell pathogenesis, and strong macrophage activity is maintained until sensory cell degradation is complete. Collectively, these findings suggest that mature tissue macrophages on the basilar membrane are a dynamic group of cells that are capable of vigorous adaptation to changes in the local sensory epithelium environment influenced by sensory cell status. PMID:27837652

  11. Dynamic activation of basilar membrane macrophages in response to chronic sensory cell degeneration in aging mouse cochleae.

    PubMed

    Frye, Mitchell D; Yang, Weiping; Zhang, Celia; Xiong, Binbin; Hu, Bo Hua

    2017-02-01

    In the sensory epithelium, macrophages have been identified on the scala tympani side of the basilar membrane. These basilar membrane macrophages are the spatially closest immune cells to sensory cells and are able to directly respond to and influence sensory cell pathogenesis. While basilar membrane macrophages have been studied in acute cochlear stresses, their behavior in response to chronic sensory cell degeneration is largely unknown. Here we report a systematic observation of the variance in phenotypes, the changes in morphology and distribution of basilar membrane tissue macrophages in different age groups of C57BL/6J mice, a mouse model of age-related sensory cell degeneration. This study reveals that mature, fully differentiated tissue macrophages, not recently infiltrated monocytes, are the major macrophage population for immune responses to chronic sensory cell death. These macrophages display dynamic changes in their numbers and morphologies as age increases, and the changes are related to the phases of sensory cell degeneration. Notably, macrophage activation precedes sensory cell pathogenesis, and strong macrophage activity is maintained until sensory cell degradation is complete. Collectively, these findings suggest that mature tissue macrophages on the basilar membrane are a dynamic group of cells that are capable of vigorous adaptation to changes in the local sensory epithelium environment influenced by sensory cell status. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Acoustical transmission-line model of the middle-ear cavities and mastoid air cells.

    PubMed

    Keefe, Douglas H

    2015-04-01

    An acoustical transmission line model of the middle-ear cavities and mastoid air cell system (MACS) was constructed for the adult human middle ear with normal function. The air-filled cavities comprised the tympanic cavity, aditus, antrum, and MACS. A binary symmetrical airway branching model of the MACS was constructed using an optimization procedure to match the average total volume and surface area of human temporal bones. The acoustical input impedance of the MACS was calculated using a recursive procedure, and used to predict the input impedance of the middle-ear cavities at the location of the tympanic membrane. The model also calculated the ratio of the acoustical pressure in the antrum to the pressure in the middle-ear cavities at the location of the tympanic membrane. The predicted responses were sensitive to the magnitude of the viscothermal losses within the MACS. These predicted input impedance and pressure ratio functions explained the presence of multiple resonances reported in published data, which were not explained by existing MACS models.

  13. Clear cell hidradenocarcinoma of the ear helix: report of primary ear helix adnexal carcinoma with regional lymph node metastasis.

    PubMed

    Bae, Tae Hui; Kang, Shin Hyuk; Kim, Han Koo; Kim, Woo Seob; Kim, Mi Kyung

    2014-07-01

    Clear cell hidradenocarcinoma is a rare tumor of eccrine sweat gland origin that has a predilection for the head and neck. It has an indolent growth pattern and a higher incidence of regional and distant metastases. Metastasizing adnexal carcinomas are rare; thus, currently there is no uniform treatment guideline. We report a case of an 89-year-old female patient with clear cell hidradenocarcinoma manifesting in the right ear helix that metastasized to the right parotid gland who was treated by wide local excision and radiation therapy.

  14. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, Kyoung Ho; Yeo, Sang Won, E-mail: swyeo@catholic.ac.kr; Troy, Frederic A., E-mail: fatroy@ucdavis.edu

    Highlights: • PolySia expressed on neurons primarily during early stages of neuronal development. • PolySia–NCAM is expressed on neural stem cells from adult guinea pig spiral ganglion. • PolySia is a biomarker that modulates neuronal differentiation in inner ear stem cells. - Abstract: During brain development, polysialylated (polySia) neural cell adhesion molecules (polySia–NCAMs) modulate cell–cell adhesive interactions involved in synaptogenesis, neural plasticity, myelination, and neural stem cell (NSC) proliferation and differentiation. Our findings show that polySia–NCAM is expressed on NSC isolated from adult guinea pig spiral ganglion (GPSG), and in neurons and Schwann cells after differentiation of the NSC withmore » epidermal, glia, fibroblast growth factors (GFs) and neurotrophins. These differentiated cells were immunoreactive with mAb’s to polySia, NCAM, β-III tubulin, nestin, S-100 and stained with BrdU. NSC could regenerate and be differentiated into neurons and Schwann cells. We conclude: (1) polySia is expressed on NSC isolated from adult GPSG and on neurons and Schwann cells differentiated from these NSC; (2) polySia is expressed on neurons primarily during the early stage of neuronal development and is expressed on Schwann cells at points of cell–cell contact; (3) polySia is a functional biomarker that modulates neuronal differentiation in inner ear stem cells. These new findings suggest that replacement of defective cells in the inner ear of hearing impaired patients using adult spiral ganglion neurons may offer potential hope to improve the quality of life for patients with auditory dysfunction and impaired hearing disorders.« less

  15. sox2 and sox3 Play unique roles in development of hair cells and neurons in the zebrafish inner ear.

    PubMed

    Gou, Yunzi; Vemaraju, Shruti; Sweet, Elly M; Kwon, Hye-Joo; Riley, Bruce B

    2018-03-01

    Formation of neural and sensory progenitors in the inner ear requires Sox2 in mammals, and in other species is thought to rely on both Sox2 and Sox3. How Sox2 and/or Sox3 promote different fates is poorly understood. Our mutant analysis in zebrafish showed that sox2 is uniquely required for sensory development while sox3 is uniquely required for neurogenesis. Moderate misexpression of sox2 during placodal stages led to development of otic vesicles with expanded sensory and reduced neurogenic domains. However, high-level misexpression of sox2 or sox3 expanded both sensory and neurogenic domains to fill the medial and lateral halves of the otic vesicle, respectively. Disruption of medial factor pax2a eliminated the ability of sox2/3 misexpression to expand sensory but not neurogenic domains. Additionally, mild misexpression of fgf8 during placodal development was sufficient to specifically expand the zone of prosensory competence. Later, cross-repression between atoh1a and neurog1 helps maintain the sensory-neural boundary, but unlike mouse this does not require Notch activity. Together, these data show that sox2 and sox3 exhibit intrinsic differences in promoting sensory vs. neural competence, but at high levels these factors can mimic each other to enhance both states. Regional cofactors like pax2a and fgf8 also modify sox2/3 functions. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia in the mouse inner ear.

    PubMed

    Raft, Steven; Andrade, Leonardo R; Shao, Dongmei; Akiyama, Haruhiko; Henkemeyer, Mark; Wu, Doris K

    2014-06-01

    Control over ionic composition and volume of the inner ear luminal fluid endolymph is essential for normal hearing and balance. Mice deficient in either the EphB2 receptor tyrosine kinase or the cognate transmembrane ligand ephrin-B2 (Efnb2) exhibit background strain-specific vestibular-behavioral dysfunction and signs of abnormal endolymph homeostasis. Using various loss-of-function mouse models, we found that Efnb2 is required for growth and morphogenesis of the embryonic endolymphatic epithelium, a precursor of the endolymphatic sac (ES) and duct (ED), which mediate endolymph homeostasis. Conditional inactivation of Efnb2 in early-stage embryonic ear tissues disrupted cell proliferation, cell survival, and epithelial folding at the origin of the endolymphatic epithelium. This correlated with apparent absence of an ED, mis-localization of ES ion transport cells relative to inner ear sensory organs, dysplasia of the endolymph fluid space, and abnormally formed otoconia (extracellular calcite-protein composites) at later stages of embryonic development. A comparison of Efnb2 and Notch signaling-deficient mutant phenotypes indicated that these two signaling systems have distinct and non-overlapping roles in ES/ED development. Homozygous deletion of the Efnb2 C-terminus caused abnormalities similar to those found in the conditional Efnb2 null homozygote. Analyses of fetal Efnb2 C-terminus deletion heterozygotes found mis-localized ES ion transport cells only in the genetic background exhibiting vestibular dysfunction. We propose that developmental dysplasias described here are a gene dose-sensitive cause of the vestibular dysfunction observed in EphB-Efnb2 signaling-deficient mice. Published by Elsevier Inc.

  17. Ephrin-B2 governs morphogenesis of endolymphatic sac and duct epithelia in the mouse inner ear

    PubMed Central

    Raft, Steven; Andrade, Leonardo R.; Shao, Dongmei; Akiyama, Haruhiko; Henkemeyer, Mark; Wu, Doris K.

    2014-01-01

    Control over ionic composition and volume of the inner ear luminal fluid endolymph is essential for normal hearing and balance. Mice deficient in either the EphB2 receptor tyrosine kinase or the cognate transmembrane ligand ephrin-B2 (Efnb2) exhibit background strain-specific vestibular behavioral dysfunction and signs of abnormal endolymph homeostasis. Using various loss-of-function mouse models, we found that Efnb2 is required for growth and morphogenesis of the embryonic endolymphatic epithelium, a precursor of the endolymphatic sac (ES) and duct (ED), which mediate endolymph homeostasis. Conditional inactivation of Efnb2 in early-stage embryonic ear tissues disrupted cell proliferation, cell survival, and epithelial folding at the origin of the endolymphatic epithelium. This correlated with apparent absence of an ED, mis-localization of ES ion transport cells relative to inner ear sensory organs, dysplasia of the endolymph fluid space, and abnormally formed otoconia (extracellular calcite protein composites) at later stages of embryonic development. A comparison of Efnb2 and Notch signaling deficient mutant phenotypes indicated that these two signaling systems have distinct and non overlapping roles in ES/ED development. Homozygous deletion of the Efnb2 C terminus caused abnormalities similar to those found in the conditional Efnb2 null homozygote. Analyses of fetal Efnb2 C-terminus deletion heterozygotes found mis-localized ES ion transport cells only in the genetic background exhibiting vestibular dysfunction. We propose that developmental dysplasias described here are a gene dose sensitive cause of the vestibular dysfunction observed in EphB-Efnb2 signaling-deficient mice. PMID:24583262

  18. Effectiveness of Ear Splint Therapy for Ear Deformities

    PubMed Central

    2017-01-01

    Objective To present our experience with ear splint therapy for babies with ear deformities, and thereby demonstrate that this therapy is an effective and safe intervention without significant complications. Methods This was a retrospective study of 54 babies (35 boys and 19 girls; 80 ears; age ≤3 months) with ear deformities who had received ear splint therapy at the Center for Torticollis, Department of Physical Medicine and Rehabilitation, Ajou University Hospital between December 2014 and February 2016. Before the initiation of ear splint therapy, ear deformities were classified with reference to the standard terminology. We compared the severity of ear deformity before and after ear splint therapy by using the physician's ratings. We also compared the physician's ratings and the caregiver's ratings on completion of ear splint therapy. Results Among these 54 babies, 41 children (58 ears, 72.5%) completed the ear splint therapy. The mean age at initiation of therapy was 52.91±18.26 days and the treatment duration was 44.27±32.06 days. Satyr ear, forward-facing ear lobe, Darwinian notch, overfolded ear, and cupped ear were the five most common ear deformities. At the completion of therapy, the final physician's ratings of ear deformities were significantly improved compared to the initial ratings (8.28±1.44 vs. 2.51±0.92; p<0.001). There was no significant difference between the physician's ratings and the caregiver's ratings at the completion of ear splint therapy (8.28±1.44 vs. 8.0±1.61; p=0.297). Conclusion We demonstrated that ear splint therapy significantly improved ear deformities in babies, as measured by quantitative rating scales. Ear splint therapy is an effective and safe intervention for babies with ear deformities. PMID:28289646

  19. AGE-RELATED FUNCTIONAL AND HISTOPATHOLOGICAL CHANGES OF THE EAR IN THE MPS I MOUSE

    PubMed Central

    Schachern, Patricia A.; Cureoglu, Sebahattin; Tsuprun, Vladimir; Paparella, Michael M.; Whitley, Chester

    2007-01-01

    Objective Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder caused by a mutation in the gene encoding the enzyme α-L-iduronidase. This enzyme is responsible for degradation of dermatan and heparan sulfates. Enzyme deficiency results in their accumulation in lysosomes of virtually all organs, resulting in severe somatic and neurological changes. Clinical findings of otitis media with mixed hearing loss are common. Cellular and molecular mechanisms of ear pathology and hearing loss are not understood. The purpose of this study is to describe the age-related audiologic and histopathologic changes of the ear in the mouse model of MPS I. Methods Auditory brainstemresponses (ABR) were obtained to clicks and tone bursts at 1-32 kHz, and pathological changes to middle and inner ears were studied with light and electron microscopy in fifty-three mice that included: 1) wild type (+/+) - five at 2 months, five at 4 to 6 months, and five at 13 to 19 months; 2) heterozygotes (+/−) - four at 2 months; five at 4 to 6 months; and eight at 13 to 19 months; and 3) homozygotes (−/−); five at 2 months; six at 4 to 6 months; and five at 13 to 19 months. Histopathology was also done on five newborn −/− mice. Results In newborns no lysosomal storage was observed and the ear appeared age appropriately normal. In all other −/− mice, cells with lysosomal storage vacuoles were observed in spiral ligament, spiral prominence, spiral limbus, basilar membrane, epithelial and mesothelial cells of Reissner’s membrane, endothelial cells of vessels, and some ganglion cells; their number increased with aging. Hair cell loss was not observed at 2 or 6 months, but there was total loss of the organ of Corti in year-old mice. Hearing of −/− mice was significantly decreased at all ages compared to +/+ and +/−. Hearing loss progressed from mild to moderate loss at 2 months to profound at 6 months and total deafness by one year of age. Conclusions Progressive age

  20. Adult Human Nasal Mesenchymal-Like Stem Cells Restore Cochlear Spiral Ganglion Neurons After Experimental Lesion

    PubMed Central

    Bas, Esperanza; Van De Water, Thomas R.; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M.

    2014-01-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic. PMID:24172073

  1. In Vivo Analysis of Lrig Genes Reveals Redundant and Independent Functions in the Inner Ear

    PubMed Central

    del Rio, Tony; Nishitani, Allison M.; Yu, Wei-Ming; Goodrich, Lisa V.

    2013-01-01

    Lrig proteins are conserved transmembrane proteins that modulate a variety of signaling pathways from worm to humans. In mammals, there are three family members – Lrig1, Lrig2, and Lrig3 – that are defined by closely related extracellular domains with a similar arrangement of leucine rich repeats and immunoglobulin domains. However, the intracellular domains show little homology. Lrig1 inhibits EGF signaling through internalization and degradation of ErbB receptors. Although Lrig3 can also bind ErbB receptors in vitro, it is unclear whether Lrig2 and Lrig3 exhibit similar functions to Lrig1. To gain insights into Lrig gene functions in vivo, we compared the expression and function of the Lrigs in the inner ear, which offers a sensitive system for detecting effects on morphogenesis and function. We find that all three family members are expressed in the inner ear throughout development, with Lrig1 and Lrig3 restricted to subsets of cells and Lrig2 expressed more broadly. Lrig1 and Lrig3 overlap prominently in the developing vestibular apparatus and simultaneous removal of both genes disrupts inner ear morphogenesis. This suggests that these two family members act redundantly in the otic epithelium. In contrast, although Lrig1 and Lrig2 are frequently co-expressed, Lrig1−/−;Lrig2−/− double mutant ears show no enhanced structural abnormalities. At later stages, Lrig1 expression is sustained in non-sensory tissues, whereas Lrig2 levels are enhanced in neurons and sensory epithelia. Consistent with these distinct expression patterns, Lrig1 and Lrig2 mutant mice exhibit different forms of impaired auditory responsiveness. Notably, Lrig1−/−;Lrig2−/− double mutant mice display vestibular deficits and suffer from a more severe auditory defect that is accompanied by a cochlear innervation phenotype not present in single mutants. Thus, Lrig genes appear to act both redundantly and independently, with Lrig2 emerging as the most functionally distinct family

  2. Histochemical localisation of carbonic anhydrase in the inner ear of developing cichlid fish, Oreochromis mossambicus

    NASA Astrophysics Data System (ADS)

    Beier, M.; Hilbig, R.; Anken, R.

    2008-12-01

    Inner ear otolith growth in terms of mineralisation mainly depends on the enzyme carbonic anhydrase (CAH). CAH is located in specialised, mitochondria-rich macular cells (ionocytes), which are involved in the endolymphatic ion exchange, and the enzyme is responsible for the provision of the pH-value necessary for otolithic calcium carbonate deposition. In the present study, for the first time the localisation of histochemically demonstrated CAH was analysed during the early larval development of a teleost, the cichlid fish Oreochromis mossambicus. CAH-reactivity was observed already in stage 7 animals (onset of otocyst development; staging follows Anken et al. [Anken, R., Kappel, T., Slenzka, K., Rahmann, H. The early morphogenetic development of the cichlid fish, Oreochromis mossambicus (Perciformes, Teleostei). Zool. Anz. 231, 1-10, 1993]). Neuroblasts (from which sensory and supporting cells are derived) proved to be CAH-positive. Already at stage 12 (hatch), CAH-positive regions could be attributed to ionocyte containing regions both in the so-called meshwork and patches area of the macula (i.e., clearly before ionocytes can be identified on ultrastructural level or by employing immunocytochemistry). In contrast to the circumstances observed in mammalian species, sensory hair cells stained negative for CAH in the cichlid. With the onset of stage 16 (finray primordia in dorsal fin, yolk-sac being increasingly absorbed), CAH-reactivity was observed in the vestibular nerve. This indicates the onset of myelinisation and thus commencement of operation. The localisation of CAH in the inner ear of fish (especially the differences in comparison to mammals) is discussed on the basis of its role in otolith calcification. Since the vestibular system is a detector of acceleration and thus gravity, also aspects regarding effects of altered gravity on CAH and hence on the mineralisation of otoliths in an adaptive process are addressed.

  3. The plastic ear and perceptual relearning in auditory spatial perception

    PubMed Central

    Carlile, Simon

    2014-01-01

    The auditory system of adult listeners has been shown to accommodate to altered spectral cues to sound location which presumably provides the basis for recalibration to changes in the shape of the ear over a life time. Here we review the role of auditory and non-auditory inputs to the perception of sound location and consider a range of recent experiments looking at the role of non-auditory inputs in the process of accommodation to these altered spectral cues. A number of studies have used small ear molds to modify the spectral cues that result in significant degradation in localization performance. Following chronic exposure (10–60 days) performance recovers to some extent and recent work has demonstrated that this occurs for both audio-visual and audio-only regions of space. This begs the questions as to the teacher signal for this remarkable functional plasticity in the adult nervous system. Following a brief review of influence of the motor state in auditory localization, we consider the potential role of auditory-motor learning in the perceptual recalibration of the spectral cues. Several recent studies have considered how multi-modal and sensory-motor feedback might influence accommodation to altered spectral cues produced by ear molds or through virtual auditory space stimulation using non-individualized spectral cues. The work with ear molds demonstrates that a relatively short period of training involving audio-motor feedback (5–10 days) significantly improved both the rate and extent of accommodation to altered spectral cues. This has significant implications not only for the mechanisms by which this complex sensory information is encoded to provide spatial cues but also for adaptive training to altered auditory inputs. The review concludes by considering the implications for rehabilitative training with hearing aids and cochlear prosthesis. PMID:25147497

  4. Ethanol affects the development of sensory hair cells in larval zebrafish (Danio rerio).

    PubMed

    Uribe, Phillip M; Asuncion, James D; Matsui, Jonathan I

    2013-01-01

    Children born to mothers with substantial alcohol consumption during pregnancy can present a number of morphological, cognitive, and sensory abnormalities, including hearing deficits, collectively known as fetal alcohol syndrome (FAS). The goal of this study was to determine if the zebrafish lateral line could be used to study sensory hair cell abnormalities caused by exposure to ethanol during embryogenesis. Some lateral line sensory hair cells are present at 2 days post-fertilization (dpf) and are functional by 5 dpf. Zebrafish embryos were raised in fish water supplemented with varying concentrations of ethanol (0.75%-1.75% by volume) from 2 dpf through 5 dpf. Ethanol treatment during development resulted in many physical abnormalities characteristic of FAS in humans. Also, the number of sensory hair cells decreased as the concentration of ethanol increased in a dose-dependent manner. The dye FM 1-43FX was used to detect the presence of functional mechanotransduction channels. The percentage of FM 1-43-labeled hair cells decreased as the concentration of ethanol increased. Methanol treatment did not affect the development of hair cells. The cell cycle markers proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) demonstrated that ethanol reduced the number of sensory hair cells, as a consequence of decreased cellular proliferation. There was also a significant increase in the rate of apoptosis, as determined by TUNEL-labeling, in neuromasts following ethanol treatment during larval development. Therefore, zebrafish are a useful animal model to study the effects of hair cell developmental disorders associated with FAS.

  5. Inner ear manifestations in CHARGE: Abnormalities, treatments, animal models, and progress toward treatments in auditory and vestibular structures.

    PubMed

    Choo, Daniel I; Tawfik, Kareem O; Martin, Donna M; Raphael, Yehoash

    2017-12-01

    The inner ear contains the sensory organs for hearing and balance. Both hearing and balance are commonly affected in individuals with CHARGE syndrome (CS), an autosomal dominant condition caused by heterozygous pathogenic variants in the CHD7 gene. Semicircular canal dysplasia or aplasia is the single most prevalent feature in individuals with CHARGE leading to deficient gross motor skills and ambulation. Identification of CHD7 as the major gene affected in CHARGE has enabled acceleration of research in this field. Great progress has been made in understanding the role of CHD7 in the development and function of the inner ear, as well as in related organs such as the middle ear and auditory and vestibular neural pathways. The goals of current research on CHD7 and CS are to (a) improve our understanding of the pathology caused by CHD7 pathogenic variants and (b) to provide better tools for prognosis and treatment. Current studies utilize cells and whole animals, from flies to mammals. The mouse is an excellent model for exploring mechanisms of Chd7 function in the ear, given the evolutionary conservation of ear structure, function, Chd7 expression, and similarity of mutant phenotypes between mice and humans. Newly recognized developmental functions for mouse Chd7 are shedding light on how abnormalities in CHD7 might lead to CS symptoms in humans. Here we review known human inner ear phenotypes associated with CHD7 pathogenic variants and CS, summarize progress toward diagnosis and treatment of inner ear-related pathologies, and explore new avenues for treatment based on basic science discoveries. © 2017 Wiley Periodicals, Inc.

  6. Classification of Newborn Ear Malformations and their Treatment with the EarWell Infant Ear Correction System.

    PubMed

    Daniali, Lily N; Rezzadeh, Kameron; Shell, Cheryl; Trovato, Matthew; Ha, Richard; Byrd, H Steve

    2017-03-01

    A single practice's treatment protocol and outcomes following molding therapy on newborn ear deformations and malformations with the EarWell Infant Ear Correction System were reviewed. A classification system for grading the severity of constricted ear malformations was created on the basis of anatomical findings. A retrospective chart/photograph review of a consecutive series of infants treated with the EarWell System from 2011 to 2014 was undertaken. The infants were placed in either deformation or malformation groups. Three classes of malformation were identified. Data regarding treatment induction, duration of treatment, and quality of outcome were collected for all study patients. One hundred seventy-five infant ear malformations and 303 infant ear deformities were treated with the EarWell System. The average age at initiation of treatment was 12 days; the mean duration of treatment was 37 days. An average of six office visits was required. Treated malformations included constricted ears [172 ears (98 percent)] and cryptotia [three ears (2 percent)]. Cup ear (34 ears) was considered a constricted malformation, in contrast to the prominent ear deformity. Constricted ears were assigned to one of three classes, with each subsequent class indicating increasing severity: class I, 77 ears (45 percent); class II, 81 ears (47 percent); and class III, 14 ears (8 percent). Molding therapy with the EarWell System reduced the severity by an average of 1.2 points (p < 0.01). Complications included minor superficial excoriations and abrasions. The EarWell System was shown to be effective in eliminating or reducing the need for surgery in all but the most severe malformations. Therapeutic, IV.

  7. Characterizing human stem cell-derived sensory neurons at the single-cell level reveals their ion channel expression and utility in pain research.

    PubMed

    Young, Gareth T; Gutteridge, Alex; Fox, Heather DE; Wilbrey, Anna L; Cao, Lishuang; Cho, Lily T; Brown, Adam R; Benn, Caroline L; Kammonen, Laura R; Friedman, Julia H; Bictash, Magda; Whiting, Paul; Bilsland, James G; Stevens, Edward B

    2014-08-01

    The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell-derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders.

  8. New insights into the brain, braincase, and ear region of tyrannosaurs (Dinosauria, Theropoda), with implications for sensory organization and behavior.

    PubMed

    Witmer, Lawrence M; Ridgely, Ryan C

    2009-09-01

    The braincase region of tyrannosaurs was investigated to provide insights on anatomical attributes relevant to inferences of sensory biology and behavior. CT scanning focused on three specimens of Tyrannosaurus rex, a juvenile Gorgosaurus, and the controversial Cleveland skull (CMNH 7541). Analysis shows that the cerebral hemispheres were enlarged, but conflicting information on the optic lobes suggests that brain conformation was not fully avian. Previous estimates of olfactory bulb size for T. rex were much too large, but even the corrected sizes are relatively larger than other theropods, suggesting that odor detection was indeed of particular importance to tyrannosaurs. The inner ears show a number of coelurosaurian traits, such as elongate and rounded and rostral, lateral semicircular canals, and incipient twisting of the common crus, which we interpret to be related to enhanced reflexes coordinating rapid eye and head movements. The cochlea is elongate, which, coupled with the finding of extensive tympanic pneumaticity, supports the inference of behavioral emphasis of low-frequency sounds. Three main groups of sinuses pneumatized the braincase, and there are a number of perhaps systematically relevant differences. Orientation of the endosseous labyrinth reveals that alert head postures of T. rex and Gorgosaurus were somewhat depressed below the horizontal, but the Cleveland skull had a very strongly down-turned posture. It is concluded that tyrannosaur sensory biology is consistent with their predatory coelurosaurian heritage, with emphasis on relatively quick, coordinated eye and head movements, and probably sensitive low-frequency hearing; tyrannosaurs apomorphically enhanced their olfactory apparatus. The taxonomic status of the Cleveland skull remains unresolved. (c) 2009 Wiley-Liss, Inc.

  9. Anatomical influences on internally coupled ears in reptiles.

    PubMed

    Young, Bruce A

    2016-10-01

    Many reptiles, and other vertebrates, have internally coupled ears in which a patent anatomical connection allows pressure waves generated by the displacement of one tympanic membrane to propagate (internally) through the head and, ultimately, influence the displacement of the contralateral tympanic membrane. The pattern of tympanic displacement caused by this internal coupling can give rise to novel sensory cues. The auditory mechanics of reptiles exhibit more anatomical variation than in any other vertebrate group. This variation includes structural features such as diverticula and septa, as well as coverings of the tympanic membrane. Many of these anatomical features would likely influence the functional significance of the internal coupling between the tympanic membranes. Several of the anatomical components of the reptilian internally coupled ear are under active motor control, suggesting that in some reptiles the auditory system may be more dynamic than previously recognized.

  10. Ear Infection (Middle Ear)

    MedlinePlus

    ... secretions from the middle ear Swelling, inflammation and mucus in the eustachian tubes from an upper respiratory ... your baby for at least six months. Breast milk contains antibodies that may offer protection from ear ...

  11. Ear surgery techniques results on hearing threshold improvement

    PubMed Central

    Mokhtarinejad, Farhad; Pour, Saeed Soheili; Nilforoush, Mohammad Hussein; Sepehrnejad, Mahsa; Mirelahi, Susan

    2013-01-01

    Background: Bone conduction (BC) threshold depression is not always by means of sensory neural hearing loss and sometimes it is an artifact caused by middle ear pathologies and ossicular chain problems. In this research, the influences of ear surgeries on bone conduction were evaluated. Materials and Methods: This study was conducted as a clinical trial study. The ear surgery performed on 83 patients classified in four categories: Stapedectomy, tympanomastoid surgery and ossicular reconstruction partially or totally; Partial Ossicular Replacement Prosthesis (PORP) and Total Ossicular Replacement Prosthesis (TORP). Bone conduction thresholds assessed in frequencies of 250, 500, 1000, 2000 and 4000 Hz pre and post the surgery. Results: In stapedectomy group, the average of BC threshold in all frequencies improved approximately 6 dB in frequency of 2000 Hz. In tympanomastoid group, BC threshold in the frequency of 500, 1000 and 2000 Hz changed 4 dB (P-value < 0.05). Moreover, In the PORP group, 5 dB enhancement was seen in 1000 and 2000 Hz. In TORP group, the results confirmed that BC threshold improved in all frequencies especially at 4000 Hz about 6.5 dB. Conclusion: In according to results of this study, BC threshold shift was seen after several ear surgeries such as stapedectomy, tympanoplasty, PORP and TORP. The average of BC improvement was approximately 5 dB. It must be considered that BC depression might happen because of ossicular chain problems. Therefore; by resolving middle ear pathologies, the better BC threshold was obtained, the less hearing problems would be faced. PMID:24381615

  12. Chemical Ototoxicity of the Fish Inner Ear and Lateral Line.

    PubMed

    Coffin, Allison B; Ramcharitar, John

    2016-01-01

    Hair cell-driven mechanosensory systems are crucial for successful execution of a number of behaviors in fishes, and have emerged as good models for exploring questions relevant to human hearing. This review focuses on ototoxic effects in the inner ear and lateral line system of fishes. We specifically examine studies where chemical ototoxins such as aminoglycoside antibiotics have been employed as tools to disable the lateral line. Lateral line ablation results in alterations to feeding behavior and orientation to water current in a variety of species. However, neither behavior is abolished in the presence of additional sensory cues, supporting the hypothesis that many fish behaviors are driven by multisensory integration. Within biomedical research, the larval zebrafish lateral line has become an important model system for understanding signaling mechanisms that contribute to hair cell death and for developing novel pharmacological therapies that protect hair cells from ototoxic damage. Furthermore, given that fishes robustly regenerate damaged hair cells, ototoxin studies in fishes have broadened our understanding of the molecular and genetic events in an innately regenerative system, offering potential targets for mammalian hair cell regeneration. Collectively, studies of fish mechanosensory systems have yielded insight into fish behavior and in mechanisms of hair cell death, protection, and regeneration.

  13. The physics of hearing: fluid mechanics and the active process of the inner ear.

    PubMed

    Reichenbach, Tobias; Hudspeth, A J

    2014-07-01

    Most sounds of interest consist of complex, time-dependent admixtures of tones of diverse frequencies and variable amplitudes. To detect and process these signals, the ear employs a highly nonlinear, adaptive, real-time spectral analyzer: the cochlea. Sound excites vibration of the eardrum and the three miniscule bones of the middle ear, the last of which acts as a piston to initiate oscillatory pressure changes within the liquid-filled chambers of the cochlea. The basilar membrane, an elastic band spiraling along the cochlea between two of these chambers, responds to these pressures by conducting a largely independent traveling wave for each frequency component of the input. Because the basilar membrane is graded in mass and stiffness along its length, however, each traveling wave grows in magnitude and decreases in wavelength until it peaks at a specific, frequency-dependent position: low frequencies propagate to the cochlear apex, whereas high frequencies culminate at the base. The oscillations of the basilar membrane deflect hair bundles, the mechanically sensitive organelles of the ear's sensory receptors, the hair cells. As mechanically sensitive ion channels open and close, each hair cell responds with an electrical signal that is chemically transmitted to an afferent nerve fiber and thence into the brain. In addition to transducing mechanical inputs, hair cells amplify them by two means. Channel gating endows a hair bundle with negative stiffness, an instability that interacts with the motor protein myosin-1c to produce a mechanical amplifier and oscillator. Acting through the piezoelectric membrane protein prestin, electrical responses also cause outer hair cells to elongate and shorten, thus pumping energy into the basilar membrane's movements. The two forms of motility constitute an active process that amplifies mechanical inputs, sharpens frequency discrimination, and confers a compressive nonlinearity on responsiveness. These features arise because the

  14. The physics of hearing: fluid mechanics and the active process of the inner ear

    NASA Astrophysics Data System (ADS)

    Reichenbach, Tobias; Hudspeth, A. J.

    2014-07-01

    Most sounds of interest consist of complex, time-dependent admixtures of tones of diverse frequencies and variable amplitudes. To detect and process these signals, the ear employs a highly nonlinear, adaptive, real-time spectral analyzer: the cochlea. Sound excites vibration of the eardrum and the three miniscule bones of the middle ear, the last of which acts as a piston to initiate oscillatory pressure changes within the liquid-filled chambers of the cochlea. The basilar membrane, an elastic band spiraling along the cochlea between two of these chambers, responds to these pressures by conducting a largely independent traveling wave for each frequency component of the input. Because the basilar membrane is graded in mass and stiffness along its length, however, each traveling wave grows in magnitude and decreases in wavelength until it peaks at a specific, frequency-dependent position: low frequencies propagate to the cochlear apex, whereas high frequencies culminate at the base. The oscillations of the basilar membrane deflect hair bundles, the mechanically sensitive organelles of the ear's sensory receptors, the hair cells. As mechanically sensitive ion channels open and close, each hair cell responds with an electrical signal that is chemically transmitted to an afferent nerve fiber and thence into the brain. In addition to transducing mechanical inputs, hair cells amplify them by two means. Channel gating endows a hair bundle with negative stiffness, an instability that interacts with the motor protein myosin-1c to produce a mechanical amplifier and oscillator. Acting through the piezoelectric membrane protein prestin, electrical responses also cause outer hair cells to elongate and shorten, thus pumping energy into the basilar membrane's movements. The two forms of motility constitute an active process that amplifies mechanical inputs, sharpens frequency discrimination, and confers a compressive nonlinearity on responsiveness. These features arise because the

  15. An in vitro model of murine middle ear epithelium.

    PubMed

    Mulay, Apoorva; Akram, Khondoker M; Williams, Debbie; Armes, Hannah; Russell, Catherine; Hood, Derek; Armstrong, Stuart; Stewart, James P; Brown, Steve D M; Bingle, Lynne; Bingle, Colin D

    2016-11-01

    Otitis media (OM), or middle ear inflammation, is the most common paediatric disease and leads to significant morbidity. Although understanding of underlying disease mechanisms is hampered by complex pathophysiology it is clear that epithelial abnormalities underpin the disease. There is currently a lack of a well-characterised in vitro model of the middle ear (ME) epithelium that replicates the complex cellular composition of the middle ear. Here, we report the development of a novel in vitro model of mouse middle ear epithelial cells (mMECs) at an air-liquid interface (ALI) that recapitulates the characteristics of the native murine ME epithelium. We demonstrate that mMECs undergo differentiation into the varied cell populations seen within the native middle ear. Proteomic analysis confirmed that the cultures secrete a multitude of innate defence proteins from their apical surface. We showed that the mMECs supported the growth of the otopathogen, nontypeable Haemophilus influenzae (NTHi), suggesting that the model can be successfully utilised to study host-pathogen interactions in the middle ear. Overall, our mMEC culture system can help to better understand the cell biology of the middle ear and improve our understanding of the pathophysiology of OM. The model also has the potential to serve as a platform for validation of treatments designed to reverse aspects of epithelial remodelling that underpin OM development. © 2016. Published by The Company of Biologists Ltd.

  16. Inner ear tissue preservation by rapid freezing: Improving fixation by high-pressure freezing and hybrid methods

    PubMed Central

    Bullen, A.; Taylor, R.R.; Kachar, B.; Moores, C.; Fleck, R.A.; Forge, A.

    2014-01-01

    In the preservation of tissues in as ‘close to life’ state as possible, rapid freeze fixation has many benefits over conventional chemical fixation. One technique by which rapid freeze-fixation can be achieved, high pressure freezing (HPF), has been shown to enable ice crystal artefact-free freezing and tissue preservation to greater depths (more than 40 μm) than other quick-freezing methods. Despite increasingly becoming routine in electron microscopy, the use of HPF for the fixation of inner ear tissue has been limited. Assessment of the quality of preservation showed routine HPF techniques were suitable for preparation of inner ear tissues in a variety of species. Good preservation throughout the depth of sensory epithelia was achievable. Comparison to chemically fixed tissue indicated that fresh frozen preparations exhibited overall superior structural preservation of cells. However, HPF fixation caused characteristic artefacts in stereocilia that suggested poor quality freezing of the actin bundles. The hybrid technique of pre-fixation and high pressure freezing was shown to produce cellular preservation throughout the tissue, similar to that seen in HPF alone. Pre-fixation HPF produced consistent high quality preservation of stereociliary actin bundles. Optimising the preparation of samples with minimal artefact formation allows analysis of the links between ultrastructure and function in inner ear tissues. PMID:25016142

  17. Hearing after congenital deafness: central auditory plasticity and sensory deprivation.

    PubMed

    Kral, A; Hartmann, R; Tillein, J; Heid, S; Klinke, R

    2002-08-01

    The congenitally deaf cat suffers from a degeneration of the inner ear. The organ of Corti bears no hair cells, yet the auditory afferents are preserved. Since these animals have no auditory experience, they were used as a model for congenital deafness. Kittens were equipped with a cochlear implant at different ages and electro-stimulated over a period of 2.0-5.5 months using a monopolar single-channel compressed analogue stimulation strategy (VIENNA-type signal processor). Following a period of auditory experience, we investigated cortical field potentials in response to electrical biphasic pulses applied by means of the cochlear implant. In comparison to naive unstimulated deaf cats and normal hearing cats, the chronically stimulated animals showed larger cortical regions producing middle-latency responses at or above 300 microV amplitude at the contralateral as well as the ipsilateral auditory cortex. The cortex ipsilateral to the chronically stimulated ear did not show any signs of reduced responsiveness when stimulating the 'untrained' ear through a second cochlear implant inserted in the final experiment. With comparable duration of auditory training, the activated cortical area was substantially smaller if implantation had been performed at an older age of 5-6 months. The data emphasize that young sensory systems in cats have a higher capacity for plasticity than older ones and that there is a sensitive period for the cat's auditory system.

  18. Expression of membrane-bound and cytosolic guanylyl cyclases in the rat inner ear.

    PubMed

    Seebacher, T; Beitz, E; Kumagami, H; Wild, K; Ruppersberg, J P; Schultz, J E

    1999-01-01

    Membrane-bound guanylyl cyclases (GCs) are peptide hormone receptors whereas the cytosolic isoforms are receptors for nitric oxide. In the inner ear, the membrane-bound GCs may be involved in the regulation of fluid homeostasis and the cytosolic forms possibly play a role in signal processing and regulation of local blood flow. In this comprehensive study, we examined, qualitatively and quantitatively, the transcription pattern of all known GC isoforms in the inner ear from rat by RT-PCR. The tissues used were endolymphatic sac, stria vascularis, organ of Corti, organ of Corti outer hair cells, cochlear nerve, Reissner's membrane, vestibular dark cells, and vestibular sensory cells. We show that multiple particulate (GC-A, GC-B, GC-D, GC-E, GC-F and GC-G) and several subunits of the heterodimeric cytosolic GCs (alpha1, alpha2, beta1 and beta2) are expressed, albeit at highly different levels. GC-C was not found. GC-A and the soluble subunits alpha1 and beta1 were transcribed ubiquitously. GC-B was present in all tissues except stria vascularis, which contained GC-A and traces of GC-E and GC-G. GC-B was by far the predominant membrane-bound isoform in the organ of Corti (86%), Reissner's membrane (75%) and the vestibulum (80%). Surprisingly, GC-E, a retinal isoform, was detected in significant amounts in the cochlear nerve (8%) and in the organ of Corti (4%). Although the cytosolic GC is a heterodimer composed of an alpha and a beta subunit, the mRNA transcription of these subunits was not stoichiometric. Particularly in the vestibulum, the transcription of the beta1 subunits was at least four-fold higher than of the alpha1 subunit. The data are compatible with earlier suggestions that membrane receptor GCs may be involved in the control of inner ear electrolyte and fluid composition whereas NO-stimulated GC isoforms mainly participate in the regulation of blood flow and supporting cell physiology.

  19. Animal models of middle ear cholesteatoma.

    PubMed

    Yamamoto-Fukuda, Tomomi; Takahashi, Haruo; Koji, Takehiko

    2011-01-01

    Middle ear acquired cholesteatoma is a pathological condition associated with otitis media, which may be associated with temporal bone resorption, otorrhea and hearing loss, and occasionally various other complications. Cholesteatoma is characterized by the enhanced proliferation of epithelial cells with aberrant morphologic characteristics. Unfortunately, our understanding of the mechanism underlying its pathogenesis is limited. To investigate its pathogenesis, different animal models have been used. This paper provides a brief overview of the current status of research in the field of pathogenesis of middle ear acquired cholesteatoma, four types of animal models previously reported on, up-to-date cholesteatoma research using these animal models, our current studies of the local hybrid ear model, and the future prospect of new animal models of middle ear cholesteatoma.

  20. Animal Models of Middle Ear Cholesteatoma

    PubMed Central

    Yamamoto-Fukuda, Tomomi; Takahashi, Haruo; Koji, Takehiko

    2011-01-01

    Middle ear acquired cholesteatoma is a pathological condition associated with otitis media, which may be associated with temporal bone resorption, otorrhea and hearing loss, and occasionally various other complications. Cholesteatoma is characterized by the enhanced proliferation of epithelial cells with aberrant morphologic characteristics. Unfortunately, our understanding of the mechanism underlying its pathogenesis is limited. To investigate its pathogenesis, different animal models have been used. This paper provides a brief overview of the current status of research in the field of pathogenesis of middle ear acquired cholesteatoma, four types of animal models previously reported on, up-to-date cholesteatoma research using these animal models, our current studies of the local hybrid ear model, and the future prospect of new animal models of middle ear cholesteatoma. PMID:21541229

  1. [Satellite glial cells in sensory ganglia: its role in pain].

    PubMed

    Costa, Filipa Alexandra Leite; Moreira Neto, Fani Lourença

    2015-01-01

    Satellite glial cells in sensory ganglia are a recent subject of research in the field of pain and a possible therapeutic target in the future. Therefore, the aim of this study was to summarize some of the important physiological and morphological characteristics of these cells and gather the most relevant scientific evidence about its possible role in the development of chronic pain. In the sensory ganglia, each neuronal body is surrounded by satellite glial cells forming distinct functional units. This close relationship enables bidirectional communication via a paracrine signaling between those two cell types. There is a growing body of evidence that glial satellite cells undergo structural and biochemical changes after nerve injury, which influence neuronal excitability and consequently the development and/or maintenance of pain in different animal models of chronic pain. Satellite glial cells are important in the establishment of physiological pain, in addition to being a potential target for the development of new pain treatments. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  2. Single-Cell Memory Regulates a Neural Circuit for Sensory Behavior.

    PubMed

    Kobayashi, Kyogo; Nakano, Shunji; Amano, Mutsuki; Tsuboi, Daisuke; Nishioka, Tomoki; Ikeda, Shingo; Yokoyama, Genta; Kaibuchi, Kozo; Mori, Ikue

    2016-01-05

    Unveiling the molecular and cellular mechanisms underlying memory has been a challenge for the past few decades. Although synaptic plasticity is proven to be essential for memory formation, the significance of "single-cell memory" still remains elusive. Here, we exploited a primary culture system for the analysis of C. elegans neurons and show that a single thermosensory neuron has an ability to form, retain, and reset a temperature memory. Genetic and proteomic analyses found that the expression of the single-cell memory exhibits inter-individual variability, which is controlled by the evolutionarily conserved CaMKI/IV and Raf pathway. The variable responses of a sensory neuron influenced the neural activity of downstream interneurons, suggesting that modulation of the sensory neurons ultimately determines the behavioral output in C. elegans. Our results provide proof of single-cell memory and suggest that the individual differences in neural responses at the single-cell level can confer individuality. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Damage and Recovery of Hair Cells in Fish Canal (But Not Superficial) Neuromasts after Gentamicin Exposure

    NASA Technical Reports Server (NTRS)

    Song, Jiakun; Yan, Hong Young; Popper, Arthur N.

    1995-01-01

    Recent evidence demonstrating the presence of two types of sensory hair cells in the ear of a telcost fish (Astronotus ocellatus, the oscar) indicates that hair cell heterogeneity may exist not only in amniotic vertebrates but also in anamniotes. Here we report that a similar heterogeneity between hair cell types may also occur in the other mechanosensory organ of the oscar, the lateral line. We exposed oscars to the aminoglycoside (ototoxic) antibiotic gentamicin sulfate and found damaged sensory hair cells in one class of the lateral line receptors, the canal neuromasts, but not in the other class, the superficial neuromasts. This effect was not due to the canal environment. Moreover, new ciliary bundles on hair cells of the canal neuromasts were found after, and during, gentamicin exposure. The pattern of hair cell destruction and recovery in canal neuromasts is similar to that of type 1-like hair cells found in the striolar region of the utricle and lagena of the oscar after gentamicin treatment. These results suggest that the hair cells in the canal and superficial neuromasts may be similar to type 1-like and type 2 hair cells, respectively, in the fish ear.

  4. Pathogenesis of Middle Ear Cholesteatoma

    PubMed Central

    Yamamoto-Fukuda, Tomomi; Hishikawa, Yoshitaka; Shibata, Yasuaki; Kobayashi, Toshimitsu; Takahashi, Haruo; Koji, Takehiko

    2010-01-01

    Middle ear cholesteatoma is characterized by enhanced proliferation of epithelial cells with aberrant morphological characteristics. To investigate the origin of the cholesteatoma cells, we analyzed spontaneously occurring cholesteatomas associated with a new transplantation model in Mongolian gerbils (gerbils). Cholesteatomas were induced in gerbils with a transplanted tympanic membrane by using the external auditory canal (EAC) ligation method. After the pars flaccida of the tympanic membranes were completely removed from male gerbils, corresponding portions of tympanic membranes of female gerbils were transplanted to the area of defect, and then we ligated the EAC (hybrid-model group). As a control group, the EAC of normal male and female gerbils was ligated without myringoplasty. In all ears of each group, the induced cholesteatomas were seen. In situ PCR was then performed to detect the mouse X chromosome-linked phosphoglycerate kinase-1 (pgk-1) gene on the paraffin sections. One pgk-1 spot in the epithelial nuclei was detected in male cholesteatoma, and two pgk-1 spots were detected in female cholesteatoma, respectively. On the other hand, in the hybrid-model group, we detected not only one but also two pgk-1 spots in the epithelial nuclei of cholesteatoma. These results strengthened the evidence that the origin of epithelial cells in cholesteatoma is the tympanic membrane in this model, but not the residential middle ear epithelial cells or the skin of the EAC. PMID:20413684

  5. Investigation of Notch Signaling during Spontaneous Regeneration of Cochlear Hair Cells

    DTIC Science & Technology

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0475 TITLE: Investigation of Notch Signaling during Spontaneous Regeneration of Cochlear Hair Cells PRINCIPAL...Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Investigation of Notch Signaling during Spontaneous Regeneration of Cochlear Hair Cells 5b...inherent to military settings. These noise exposures damage and kill sensory hair cells (HCs) found in the cochlea of the inner ear, resulting in permanent

  6. Ear discharge

    MedlinePlus

    ... swabs or other small objects into the ear Middle ear infection Other causes of ear discharge include: Eczema ... tube surgery - what to ask your doctor Images Ear anatomy Eardrum repair - series References Bauer CA, Jenkins HA. Otologic symptoms and syndromes. In: Flint PW, Haughey BH, Lund V, et ...

  7. In vivo over-expression of KGF mimic human middle ear cholesteatoma.

    PubMed

    Yamamoto-Fukuda, Tomomi; Akiyama, Naotaro; Shibata, Yasuaki; Takahashi, Haruo; Ikeda, Tohru; Koji, Takehiko

    2015-10-01

    We reported previously that keratinocyte growth factor (KGF), a mesenchymal cell-derived paracrine growth factor, plays an important role in middle ear cholesteatoma formation, which is characterized by marked proliferation of epithelial cells. Here, we investigated whether KGF, the main factor that induces cholesteatoma, overexpression in vivo results in the formation of cholesteatoma. Flag-hKGF cDNA driven by CMV14 promoter was transfected through electroporation into the external auditory canal (EAC) of rats once (short-term model) or five times on every fourth day (long-term model). Ears transfected with empty vector were used as controls. Successful transfection of plasmids into epithelial and stromal cells was confirmed by Flag immunohistochemistry. In the short-term model, the intensity of KGF protein was the strongest in hKGF transfected ear at day 4. KGF expression induced epithelial cell proliferation, reaching a peak level at day 4 and then decreased later, while in the long-term model, KGF expression in the EAC led to middle ear cholesteatoma formation. In conclusion, we described here a new experimental model of human middle ear cholesteatoma, and demonstrated that KGF and KGF receptor paracrine action play an essential role in middle ear cholesteatoma formation in an in vivo model.

  8. Ear wax

    MedlinePlus

    See your provider if your ears are blocked with wax and you are unable to remove the wax. Also call if you have an ear wax blockage and you develop new symptoms, such as: Drainage from the ear Ear pain Fever Hearing loss that continues after you clean the wax

  9. Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles

    PubMed Central

    Sayed, Zafar A.; Stephanopoulos, Nicholas; Berns, Eric J.; Wadhwani, Anil R.; Morrissey, Zachery D.; Chadly, Duncan M.; Kobayashi, Shun; Edelbrock, Alexandra N.; Mashimo, Tomoji; Miller, Charles A.; McGuire, Tammy L.; Stupp, Samuel I.; Kessler, John A.

    2017-01-01

    The use of human embryonic stem cells (hESCs) for regeneration of the spiral ganglion will require techniques for promoting otic neuronal progenitor (ONP) differentiation, anchoring of cells to anatomically appropriate and specific niches, and long-term cell survival after transplantation. In this study, we used self-assembling peptide amphiphile (PA) molecules that display an IKVAV epitope (IKVAV-PA) to create a niche for hESC-derived ONPs that supported neuronal differentiation and survival both in vitro and in vivo after transplantation into rodent inner ears. A feature of the IKVAV-PA gel is its ability to form organized nanofibers that promote directed neurite growth. Culture of hESC-derived ONPs in IKVAV-PA gels did not alter cell proliferation or viability. However, the presence of IKVAV-PA gels increased the number of cells expressing the neuronal marker beta-III tubulin and improved neurite extension. The self-assembly properties of the IKVAV-PA gel allowed it to be injected as a liquid into the inner ear to create a biophysical niche for transplanted cells after gelation in vivo. Injection of ONPs combined with IKVAV-PA into the modiolus of X-SCID rats increased survival and localization of the cells around the injection site compared to controls. Human cadaveric temporal bone studies demonstrated the technical feasibility of a transmastoid surgical approach for clinical intracochlear injection of the IKVAV-PA/ONP combination. Combining stem cell transplantation with injection of self-assembling PA gels to create a supportive niche may improve clinical approaches to spiral ganglion regeneration. PMID:29284013

  10. Inner ear tissue preservation by rapid freezing: improving fixation by high-pressure freezing and hybrid methods.

    PubMed

    Bullen, A; Taylor, R R; Kachar, B; Moores, C; Fleck, R A; Forge, A

    2014-09-01

    In the preservation of tissues in as 'close to life' state as possible, rapid freeze fixation has many benefits over conventional chemical fixation. One technique by which rapid freeze-fixation can be achieved, high pressure freezing (HPF), has been shown to enable ice crystal artefact-free freezing and tissue preservation to greater depths (more than 40 μm) than other quick-freezing methods. Despite increasingly becoming routine in electron microscopy, the use of HPF for the fixation of inner ear tissue has been limited. Assessment of the quality of preservation showed routine HPF techniques were suitable for preparation of inner ear tissues in a variety of species. Good preservation throughout the depth of sensory epithelia was achievable. Comparison to chemically fixed tissue indicated that fresh frozen preparations exhibited overall superior structural preservation of cells. However, HPF fixation caused characteristic artefacts in stereocilia that suggested poor quality freezing of the actin bundles. The hybrid technique of pre-fixation and high pressure freezing was shown to produce cellular preservation throughout the tissue, similar to that seen in HPF alone. Pre-fixation HPF produced consistent high quality preservation of stereociliary actin bundles. Optimising the preparation of samples with minimal artefact formation allows analysis of the links between ultrastructure and function in inner ear tissues. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Expression of macrophage migration inhibitory factor and CD74 in the inner ear and middle ear in lipopolysaccharide-induced otitis media.

    PubMed

    Ishihara, Hisashi; Kariya, Shin; Okano, Mitsuhiro; Zhao, Pengfei; Maeda, Yukihide; Nishizaki, Kazunori

    2016-10-01

    Significant expression of macrophage migration inhibitory factor and its receptor (CD74) was observed in both the middle ear and inner ear in experimental otitis media in mice. Modulation of macrophage migration inhibitory factor and its signaling pathway might be useful in the management of inner ear inflammation due to otitis media. Inner ear dysfunction secondary to otitis media has been reported. However, the specific mechanisms involved are not clearly understood. The aim of this study is to investigate the expression of macrophage migration inhibitory factor and CD74 in the middle ear and inner ear in lipopolysaccharide-induced otitis media. BALB/c mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline (PBS). The mice were sacrificed 24 h after injection, and temporal bones were processed for polymerase chain reaction (PCR) analysis, histologic examination, and immunohistochemistry. PCR examination revealed that the lipopolysaccharide-injected mice showed a significant up-regulation of macrophage migration inhibitory factor in both the middle ear and inner ear as compared with the PBS-injected control mice. The immunohistochemical study showed positive reactions for macrophage migration inhibitory factor and CD74 in infiltrating inflammatory cells, middle ear mucosa, and inner ear in the lipopolysaccharide-injected mice.

  12. Ear Pieces

    ERIC Educational Resources Information Center

    DiJulio, Betsy

    2011-01-01

    In this article, the author describes an art project wherein students make fanciful connections between art and medicine. This project challenges students to interpret "ear idioms" (e.g. "blow it out your ear," "in one ear and out the other") by relying almost entirely on realistic ear drawings, the placement of them, marks, and values. In that…

  13. Interplay between mast cells, enterochromaffin cells, and sensory signaling in the aging human bowel.

    PubMed

    Yu, Y; Daly, D M; Adam, I J; Kitsanta, P; Hill, C J; Wild, J; Shorthouse, A; Grundy, D; Jiang, W

    2016-10-01

    Advanced age is associated with a reduction in clinical visceral pain perception. However, the underlying mechanisms remain largely unknown. Previous studies have suggested that an abnormal interplay between mast cells, enterochromaffin (EC) cells, and afferent nerves contribute to nociception in gastrointestinal disorders. The aim of this study was to investigate how aging affects afferent sensitivity and neuro-immune association in the human bowel. Mechanical and chemical sensitivity of human bowel afferents were examined by ex vivo afferent nerve recordings. Age-related changes in the density of mast cells, EC cells, sensory nerve terminals, and mast cell-nerve micro-anatomical association were investigated by histological and immune staining. Human afferents could be broadly classified into subpopulations displaying mechanical and chemical sensitivity, adaptation, chemo-sensitization, and recruitment. Interestingly human bowel afferent nerve sensitivity was attenuated with age. The density of substance P-immunoreactive (SP-IR) nerve varicosities was also reduced with age. In contrast, the density of ileal and colonic mucosal mast cells was increased with age, as was ileal EC cell number. An increased proportion of mast cells was found in close apposition to SP-IR nerves. Afferent sensitivity in human bowel was reduced with advancing age. Augmentation of mast cells and EC cell numbers and the mast cell-nerve association suggest a compensatory mechanism for sensory neurodegeneration. © 2016 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.

  14. Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy.

    PubMed

    Schwab, Andrew J; Ebert, Allison D

    2014-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.

  15. Penicillin treatment accelerates middle ear inflammation in experimental pneumococcal otitis media.

    PubMed Central

    Kawana, M; Kawana, C; Giebink, G S

    1992-01-01

    Most Streptococcus pneumoniae strains are killed by very low concentrations of penicillin and other beta-lactam antibiotics, yet middle ear inflammation and effusion persist for days to weeks after treatment in most cases of pneumococcal otitis media. To study the effect of beta-lactam antibiotic treatment on pneumococci and the middle ear inflammatory response during pneumococcal otitis media, we measured concentrations of pneumococci, inflammatory cells, and lysozyme in middle ear fluid (MEF) by using the chinchilla model. Procaine penicillin G given intramuscularly 12 and 36 h after inoculation of pneumococci into the middle ear caused a significant acceleration in the MEF inflammatory cell concentration compared with that in untreated controls, with a significant peak in the inflammatory cell concentration 24 h after pneumococcal inoculation. The lysozyme concentration in MEF also increased more rapidly in treated than in control animals. Viable pneumococci were not detected in MEF after the second dose of penicillin, but the total pneumococcal cell concentration remained unchanged for at least 45 days. Therefore, penicillin treatment accelerated middle ear inflammation while killing pneumococci, but treatment did not accelerate clearance of the nonviable pneumococcal cells from MEF. Further studies will need to define the contribution of these responses to acute and chronic tissue injury. PMID:1563782

  16. Ear wax

    PubMed Central

    2008-01-01

    Introduction Ear wax only becomes a problem if it causes a hearing impairment or other ear-related symptoms. Ear wax is more likely to accumulate and cause a hearing impairment when normal extrusion is prevented — for example, by the use of hearing aids, or by the use of cotton buds to clean the ears. Ear wax can visually obscure the ear drum, and may need to be removed for diagnostic purposes. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of methods to remove ear wax? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found nine systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: ear syringing; manual removal (other than ear syringing); and wax softeners (alone or prior to syringing). PMID:19450340

  17. Ear Disorders

    MedlinePlus

    ... most common illness in infants and young children. Tinnitus, a roaring in your ears, can be the ... problems in your inner ear; its symptoms include tinnitus and dizziness. Ear barotrauma is an injury to ...

  18. Requirement for Lmo4 in the Vestibular Morphogenesis of Mouse Inner Ear

    PubMed Central

    Deng, Min; Pan, Ling; Xie, Xiaoling; Gan, Lin

    2009-01-01

    During development, compartmentalization of an early embryonic structure produces blocks of cells with distinct properties and developmental potentials. The auditory and vestibular components of vertebrate inner ears are derived from defined compartments within the otocyst during embryogenesis. The vestibular apparatus, including three semicircular canals, saccule, utricle, and their associated sensory organs, detects angular and linear acceleration of the head and relays the information through vestibular neurons to vestibular nuclei in the brainstem. How the early developmental events manifest vestibular structures at the molecular level is largely unknown. Here, we show that LMO4, a LIM-domain-only transcriptional regulator, is required for the formation of semicircular canals and their associated sensory cristae. Targeted disruption of Lmo4 resulted in the dysmorphogenesis of the vestibule and in the absence of three semicircular canals, anterior and posterior cristae. In Lmo4-null otocysts, canal outpouches failed to form and cell proliferation was reduced in the dorsolateral region. Expression analysis of the known otic markers showed that Lmo4 is essential for the normal expression of Bmp4, Fgf10, Msx1, Isl1, Gata3, and Dlx5 in the dorsolateral domain of the otocyst, whereas the initial compartmentalization of the otocyst remains unaffected. Our results demonstrate that Lmo4 controls the development of the dorsolateral otocyst into semicircular canals and cristae through two distinct mechanisms: regulating the expression of otic specific genes and stimulating the proliferation of the dorsolateral part of the otocyst. PMID:19913004

  19. The comparative anatomy of the pig middle ear cavity: a model for middle ear inflammation in the human?

    PubMed Central

    PRACY, J. P.; WHITE, A.; MUSTAFA, Y.; SMITH, D.; PERRY, M. E.

    1998-01-01

    This study was undertaken to develop a functional model of otitis media with effusion (OME) in the pig (Sus scrofa), with the purpose of investigating the origin of lymphocytes populating the middle ear during the course of an inflammatory process. The relevance of the model to the human condition of OME is to a large extent dependent on the anatomical and physiological similarities between the middle ear cavity and the pharyngeal lymphoid tissue of the pig and man. Anatomical specimens were collected from 7 young Large White pigs to determine the gross anatomy of the middle ear cavity and the histological characteristics of the middle ear mucosa. It was found that the anatomy of the 3 parts of the middle ear cavity in man and in the pig is broadly similar, although some minor differences were observed. The porcine eustachian tube was seen to be cartilaginous throughout its length in contrast to the part osseous, part cartilaginous structure found in man; the porcine ossicles were slightly different in shape to those of man and the air cell system was situated inferior to the tympanic cavity in the pig as opposed to posteriorly in man. This paper describes the structure and morphology of the pig middle ear cavity and compares and contrasts it with that of man. The minor differences observed are of anatomical importance but do not diminish the usefulness of the pig middle ear cleft as a potential model for human middle ear disorders. PMID:9688502

  20. Swimmer's Ear

    MedlinePlus

    ... Eardrum Taking Care of Your Ears Can Loud Music Hurt My Ears? Your Ears What's Earwax? How Do Pain Relievers Work? View more About Us Contact Us Partners Editorial Policy Permissions Guidelines Privacy Policy & Terms of Use Notice ...

  1. Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-Jun-N-terminal kinase signaling.

    PubMed

    Eshraghi, Adrien A; Gupta, Chhavi; Van De Water, Thomas R; Bohorquez, Jorge E; Garnham, Carolyn; Bas, Esperanza; Talamo, Victoria Maria

    2013-03-01

    To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM-111. An animal model of cochlear implantation. Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM-111 30 minutes before EIT (EIT+AM-111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)-phalloidin staining for hair cell counts were performed at 90 days post-EIT. Immunostaining for 4-hydroxy-2-nonenal (HNE), activated caspase-3, CellROX, and phospho-c-Jun were performed at 24 hours post-EIT. ABR thresholds increased post-EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM-111 treated or unoperated control ears. AM-111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post-EIT. Immunostaining of 24-hour post-EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase-3 was observed only in SCs, and phosphorylation of c-Jun occurred only in HCs of the EIT-only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase-3, or phospho-c-Jun in the organ of Corti specimens from AM-111 treated cochleae. Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM-111 provided a significant level of protection against EIT-induced hearing losses, HC losses, and damage to neural elements. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  2. Cell Growth Characteristics, Differentiation Frequency, and Immunophenotype of Adult Ear Mesenchymal Stem Cells

    PubMed Central

    Staszkiewicz, Jaroslaw; Frazier, Trivia P.; Rowan, Brian G.; Bunnell, Bruce A.; Chiu, Ernest S.; Gimble, Jeffrey M.

    2010-01-01

    Ear mesenchymal stem cells (EMSCs) represent a readily accessible population of stem-like cells that are adherent, clonogenic, and have the ability to self-renew. Previously, we have demonstrated that they can be induced to differentiate into adipocyte, osteocyte, chondrocyte, and myocyte lineages. The purpose of the current study was to characterize the growth kinetics of the cells and to determine their ability to form colonies of fibroblasts, adipocytes, osteocytes, and chondrocytes. In addition, the immunophenotypes of freshly isolated and culture-expanded cells were evaluated. From 1 g of tissue, we were able to isolate an average of 7.8 × 106 cells exhibiting a cell cycle length of ∼2–3 days. Colony-forming unit (CFU) assays indicated high proliferation potential, and confirmed previously observed multipotentiality of the cells. Fluorescence-activated cell sorting (FACS) showed that EMSCs were negative for hematopoietic markers (CD4, CD45), proving that they did not derive from circulating hematopoietic cells. The FACS analyses also showed high expression of stem cell antigen-1 (Sca-1) with only a minor population of cells expressing CD117, thus identifying Sca-1 as the more robust stem cell biomarker. Additionally, flow cytometry data revealed that the expression patterns of hematopoietic, stromal, and stem cell markers were maintained in the passaged EMSCs, consistent with the persistence of an undifferentiated state. This study indicates that EMSCs provide an alternative model for in vitro analyses of adult mesenchymal stem cells (MSCs). Further studies will be necessary to determine their utility for tissue engineering and regenerative medical applications. PMID:19400629

  3. Wnt Responsive Lgr5-Expressing Stem Cells Are Hair Cell Progenitors in the Cochlea

    PubMed Central

    Shi, Fuxin; Kempfle, Judith; Edge, Albert S. B.

    2012-01-01

    Auditory hair cells are surrounded on their basolateral aspects by supporting cells, and these two cell types together constitute the sensory epithelium of the organ of Corti, which is the hearing apparatus of the ear. We show here that Lgr5, a marker for adult stem cells, was expressed in a subset of supporting cells in the newborn and adult murine cochlea. Lgr5-expressing supporting cells, sorted by flow cytometry and cultured in a single cell suspension, as compared to unsorted cells, displayed an enhanced capacity for self-renewing neurosphere formation in response to Wnt and were converted to hair cells at a higher (>10-fold) rate. The greater differentiation of hair cell in the neurosphere assay showed that Lgr5-positive cells had the capacity to act as cochlear progenitor cells, and lineage tracing confirmed that Lgr5-expressing cells accounted for the cells that formed neurospheres and differentiated to hair cells. The responsiveness to Wnt of cells with a capacity for division and sensory cell formation suggests a potential route to new hair cell generation in the adult cochlea. PMID:22787049

  4. Optimization of gene delivery methods in Xenopus laevis kidney (A6) and Chinese hamster ovary (CHO) cell lines for heterologous expression of Xenopus inner ear genes

    PubMed Central

    Ramirez-Gordillo, Daniel; Trujillo-Provencio, Casilda; Knight, V. Bleu; Serrano, Elba E.

    2014-01-01

    The Xenopus inner ear provides a useful model for studies of hearing and balance because it shares features with the mammalian inner ear, and because amphibians are capable of regenerating damaged mechanosensory hair cells. The structure and function of many proteins necessary for inner ear function have yet to be elucidated and require methods for analysis. To this end, we seek to characterize Xenopus inner ear genes outside of the animal model through heterologous expression in cell lines. As part of this effort, we aimed to optimize physical (electroporation), chemical (lipid-mediated; Lipofectamine™ 2000, Metafectene® Pro), and biological (viral-mediated; BacMam virus Cellular Lights™ Tubulin-RFP) gene delivery methods in amphibian (Xenopus; A6) cells and mammalian (Chinese hamster ovary (CHO)) cells. We successfully introduced the commercially available pEGFP-N3, pmCherry-N1, pEYFP-Tubulin, and Cellular Lights™ Tubulin-RFP fluorescent constructs to cells and evaluated their transfection or transduction efficiencies using the three gene delivery methods. In addition, we analyzed the transfection efficiency of a novel construct synthesized in our laboratory by cloning the Xenopus inner ear calcium-activated potassium channel β1 subunit, then subcloning the subunit into the pmCherry-N1 vector. Every gene delivery method was significantly more effective in CHO cells. Although results for the A6 cell line were not statistically significant, both cell lines illustrate a trend towards more efficient gene delivery using viral-mediated methods; however the cost of viral transduction is also much higher. Our findings demonstrate the need to improve gene delivery methods for amphibian cells and underscore the necessity for a greater understanding of amphibian cell biology. PMID:21959846

  5. Alternative splicing of inner-ear-expressed genes.

    PubMed

    Wang, Yanfei; Liu, Yueyue; Nie, Hongyun; Ma, Xin; Xu, Zhigang

    2016-09-01

    Alternative splicing plays a fundamental role in the development and physiological function of the inner ear. Inner-ear-specific gene splicing is necessary to establish the identity and maintain the function of the inner ear. For example, exon 68 of Cadherin 23 (Cdh23) gene is subject to inner-ear-specific alternative splicing, and as a result, Cdh23(+ 68) is only expressed in inner ear hair cells. Alternative splicing along the tonotopic axis of the cochlea contributes to frequency tuning, particularly in lower vertebrates, such as chickens and turtles. Differential splicing of Kcnma1, which encodes for the α subunit of the Ca(2+)-activated K(+) channel (BK channel), has been suggested to affect the channel gating properties and is important for frequency tuning. Consequently, deficits in alternative splicing have been shown to cause hearing loss, as we can observe in Bronx Waltzer (bv) mice and Sfswap mutant mice. Despite the advances in this field, the regulation of alternative splicing in the inner ear remains elusive. Further investigation is also needed to clarify the mechanism of hearing loss caused by alternative splicing deficits.

  6. Synaptic communication and signal processing among sensory cells in taste buds.

    PubMed

    Chaudhari, Nirupa

    2014-08-15

    Taste buds (sensory structures embedded in oral epithelium) show a remarkable diversity of transmitters synthesized and secreted locally. The known transmitters accumulate in a cell type selective manner, with 5-HT and noradrenaline being limited to presynaptic cells, GABA being synthesized in both presynaptic and glial-like cells, and acetylcholine and ATP used for signalling by receptor cells. Each of these transmitters participates in local negative or positive feedback circuits that target particular cell types. Overall, the role of ATP is the best elucidated. ATP serves as a principal afferent transmitter, and also is the key trigger for autocrine positive feedback and paracrine circuits that result in potentiation (via adenosine) or inhibition (via GABA or 5-HT). While many of the cellular receptors and mechanisms for these circuits are known, their impact on sensory detection and perception remains to be elaborated in most instances. This brief review examines what is known, and some of the open questions and controversies surrounding the transmitters and circuits of the taste periphery. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  7. Ear Scaffold Reconstruction Using Ultrasonic Aspirator for Cauliflower Ear.

    PubMed

    Hao, Scarlett; Angster, Kristen; Hubbard, Fleesie; Greywoode, Jewel; Vakharia, Kalpesh T

    2018-04-01

    Untreated auricular hematomas from ear trauma can result in an ear deformation known as cauliflower ear, secondary to fibrosis and new cartilage overgrowth. Cauliflower ear reconstruction has traditionally utilized tools such as a drill or a scalpel in order to improve auricular cosmesis. We present a case report utilizing an ultrasonic aspirator to recontour the fibrosed cartilage of a cauliflower ear. The ultrasonic aspirator has advantages over traditional tools in its ability to provide finely controlled bone removal without damage to surrounding soft tissue. The patient in this case report underwent multistage reconstruction using the ultrasonic aspirator with excellent cosmetic result and patient satisfaction.

  8. [Atypical inflammation of the middle ear].

    PubMed

    Garov, E V; Kryukov, A I; Zelenkova, V N; Sidorina, N G; Kaloshina, A S

    The objective of the present study was to characterize the patients presenting with atypical inflammation of the middle ear and consider the currently available methods for their examination. A total of 20 patients at the age from 16 to 66 years were admitted to the Department of Ear Microsurgery during the period from 2008 and 2016 for the treatment of atypical inflammation of the middle ear. Eleven of them (18 ears) were found to have tuberculous lesions (TL) of the middle ear while the remaining 9 patients (11 ears) suffered giant cell vasculitis (GCV). All the patients underwent the general clinical and otorhinolaryngological examination, computed tomography of the temporal bones and the thoracic cavity organs, cytological, bacteriological, pathomorphological, and molecular-genetic studies including PCR diagnostics, rheumatological tests, as well as counseling by a phthisiotherapist and rheumatologist. The primary localization of TL in the middle ear was documented in 6 patients including its association with lung lesions in 5 cases. The clinical picture of the disease in 5 patients was that of smoldering exudative pathology and in 6 ones was accompanied by suppurative perforative otitis media. According to the laboratory analyses, bacteriological diagnostics proved efficient in 9% of the patients, pathomorphological and cytological diagnostics in 18% and 27.3% of the cases respectively while the effectiveness of PCR diagnostics was estimated at 55%. The diagnosis in individual patients was established within the period from 1 month to 1.5 years after they first sought medical advice in connection with complaints of the ear disease. Tuberculosis of the middle ear began to develop as exudative middle otitis that acquired the form of bilateral pathology in 4 patients. Three patients had a concomitant pulmonary disease. In 4 patuents, the diagnois of middle ear tuberculosis was established based on the presence of the specific antibodies and in 5 ones based on the

  9. Ear Problems

    MedlinePlus

    ... may have OTITIS MEDIA, an infection of the middle ear. Self CareSee your doctor. Many ear infections will ... half-alcohol, half-white vinegar solution in the ear before and after swimming or ... JOINT (TMJ) SYNDROME, a disorder that affects the jaw joint, may ...

  10. Rhesus Cochlear and Vestibular Functions Are Preserved After Inner Ear Injection of Saline Volume Sufficient for Gene Therapy Delivery.

    PubMed

    Dai, Chenkai; Lehar, Mohamed; Sun, Daniel Q; Rvt, Lani Swarthout; Carey, John P; MacLachlan, Tim; Brough, Doug; Staecker, Hinrich; Della Santina, Alexandra M; Hullar, Timothy E; Della Santina, Charles C

    2017-08-01

    reconstruction of computed tomography (CT) images of adult C57BL6 mouse, rat, rhesus macaque, and human temporal bones (N = 3 each). Injection was well tolerated by all animals, with eight of nine exhibiting no signs of disequilibrium and one animal exhibiting transient disequilibrium that resolved spontaneously by 24 h after surgery. Physiologic results at the final, 8-week post-injection measurement showed that injection was well tolerated. Compared to its pretreatment values, no treated ear's ABR threshold had worsened by more than 5 dB at any stimulus frequency; distortion product otoacoustic emissions remained detectable above the noise floor for every treated ear (mean, SD and maximum deviation from baseline: -1.3, 9.0, and -18 dB, respectively); and no animal exhibited a reduction of more than 3 % in vestibulo-ocular reflex gain during high-acceleration, whole-body, passive yaw rotations in darkness toward the treated side. All control ears and all operated ears with definite histologic evidence of injection through the intended site showed similar findings, with intact hair cells in all five inner ear sensory epithelia and intact auditory/vestibular neurons. The relative volumes of mouse, rat, rhesus, and human inner ears as measured by CT were (mean ± SD) 2.5 ± 0.1, 5.5 ± 0.4, 59.4 ± 4.7 and 191.1 ± 4.7 μL. These results indicate that injection of PBSV at volumes sufficient for gene therapy delivery can be accomplished without destruction of inner ear structures required for hearing and vestibular sensation.

  11. Respiration Gates Sensory Input Responses in the Mitral Cell Layer of the Olfactory Bulb

    PubMed Central

    Short, Shaina M.; Morse, Thomas M.; McTavish, Thomas S.; Shepherd, Gordon M.; Verhagen, Justus V.

    2016-01-01

    Respiration plays an essential role in odor processing. Even in the absence of odors, oscillating excitatory and inhibitory activity in the olfactory bulb synchronizes with respiration, commonly resulting in a burst of action potentials in mammalian mitral/tufted cells (MTCs) during the transition from inhalation to exhalation. This excitation is followed by inhibition that quiets MTC activity in both the glomerular and granule cell layers. Odor processing is hypothesized to be modulated by and may even rely on respiration-mediated activity, yet exactly how respiration influences sensory processing by MTCs is still not well understood. By using optogenetics to stimulate discrete sensory inputs in vivo, it was possible to temporally vary the stimulus to occur at unique phases of each respiration. Single unit recordings obtained from the mitral cell layer were used to map spatiotemporal patterns of glomerular evoked responses that were unique to stimulations occurring during periods of inhalation or exhalation. Sensory evoked activity in MTCs was gated to periods outside phasic respiratory mediated firing, causing net shifts in MTC activity across the cycle. In contrast, odor evoked inhibitory responses appear to be permitted throughout the respiratory cycle. Computational models were used to further explore mechanisms of inhibition that can be activated by respiratory activity and influence MTC responses. In silico results indicate that both periglomerular and granule cell inhibition can be activated by respiration to internally gate sensory responses in the olfactory bulb. Both the respiration rate and strength of lateral connectivity influenced inhibitory mechanisms that gate sensory evoked responses. PMID:28005923

  12. Malformation of stria vascularis in the developing inner ear of the German waltzing guinea pig.

    PubMed

    Jin, Zhe; Mannström, Paula; Järlebark, Leif; Ulfendahl, Mats

    2007-05-01

    Auditory function and cochlear morphology have previously been described in the postnatal German waltzing guinea pig, a strain with recessive deafness. In the present study, cochlear histopathology was further investigated in the inner ear of the developing German waltzing guinea pig (gw/gw). The lumen of the cochlear duct diminished progressively from embryonic day (E) 35 to E45 and was absent at E50 because of the complete collapse of Reissner's membrane onto the hearing organ. The embryonic stria vascularis, consisting of a simple epithelium, failed to transform into the complex trilaminar tissue seen in normal animals and displayed signs of degeneration. Subsequent degeneration of the sensory epithelium was observed from E50 and onwards. Defective and insufficient numbers of melanocytes were observed in the developing gw/gw stria vascularis. A gene involved in cochlear melanocyte development, Pax3, was markedly reduced in lateral wall tissue of the cochlea of both E40 and adult gw/gw individuals, whereas its expression was normal in the skin and diaphragm muscle of adult gw/gw animals. The Pax3 gene may thus be involved in the pathological process but is unlikely to be the primary mutated gene in the German waltzing guinea pig. TUNEL assay showed no signs of apoptotic cell death in the developing stria vascularis of this type of guinea pig. Thus, malformation of the stria vascularis appears to be the primary defect in the inner ear of the German waltzing guinea pig. Defective and insufficient numbers of melanocytes might migrate to the developing stria vascularis but fail to provide the proper support for the subsequent development of marginal and basal cells, thereby leading to stria vascularis malformation and dysfunction in the inner ear of the German waltzing guinea pig.

  13. Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma

    PubMed Central

    Mizutari, Kunio; Fujioka, Masato; Hosoya, Makoto; Bramhall, Naomi; Okano, Hirotaka James; Okano, Hideyuki; Edge, Albert S.B.

    2013-01-01

    SUMMARY Hearing loss due to damage to auditory hair cells is normally irreversible because mammalian hair cells do not regenerate. Here, we show that new hair cells can be induced and can cause partial recovery of hearing in ears damaged by noise trauma, when Notch signaling is inhibited by a γ-secretase inhibitor selected for potency in stimulating hair cell differentiation from inner ear stem cells in vitro. Hair cell generation resulted from an increase in the level of bHLH transcription factor, Atoh1, in response to inhibition of Notch signaling. In vivo prospective labeling of Sox2-expressing cells with a Cre/lox system unambiguously demonstrated that hair cell generation resulted from transdifferentiation of supporting cells. Manipulating cell fate of cochlear sensory cells in vivo by pharmacological inhibition of Notch signaling is thus a potential therapeutic approach to the treatment of deafness. PMID:23312516

  14. Immunolocalization of aquaporin CHIP in the guinea pig inner ear.

    PubMed

    Stanković, K M; Adams, J C; Brown, D

    1995-12-01

    Aquaporin CHIP (AQP-CHIP) is a water channel protein previously identified in red blood cells and water transporting epithelia. The inner ear is an organ of hearing and balance whose normal function depends critically on maintenance of fluid homeostasis. In this study, AQP-CHIP, or a close homologue, was found in specific cells of the inner ear, as assessed by immunocytochemistry with the use of affinity-purified polyclonal antibodies against AQP-CHIP.AQP-CHIP was predominantly found in fibrocytes in close association with bone, including most of the cells lining the bony labyrinth and in fibrocytes lining the endolymphatic duct and sac. AQP-CHIP-positive cells not directly apposing bone include cells under the basilar membrane, some type III fibrocytes of the spiral ligament, fibrocytes of the spiral limbus, and the trabecular perilymphatic tissue extending from the membranous to the bony labyrinth. AQP-CHIP was also found in the periosteum of the middle ear and cranial bones, as well as in chondrocytes of the oval window and stapes. The distribution of AQP-CHIP in the inner ear suggests that AQP-CHIP may have special significance for maintenance of bone and the basilar membrane, and for function of the spiral ligament.

  15. Ear Tubes

    MedlinePlus

    ... of the ear drum or eustachian tube, Down Syndrome, cleft palate, and barotrauma (injury to the middle ear caused by a reduction of air pressure, ... specialist) may be warranted if you or your child has experienced repeated ... fluid in the middle ear, barotrauma, or have an anatomic abnormality that ...

  16. An abbreviated history of the ear: from Renaissance to present.

    PubMed Central

    Hachmeister, Jorge E.

    2003-01-01

    In this article we discuss important discoveries in relation to the anatomy and physiology of the ear from Renaissance to present. Before the Renaissance, there was a paucity of knowledge of the anatomy of the ear, because of the relative inaccessibility of the temporal bone and the general perception that human dissections should not be conducted. It was not until the sixteenth century that the middle ear was described with detail. Further progress would be made between the sixteenth and eighteenth century in describing the inner ear. In the nineteenth century, technological advancement permitted a description of the cells and structures that constitute the cochlea. Von Helmholtz made further progress in hearing physiology when he postulated his resonance theory and later von Békésy when he observed a traveling wave in human cadavers within the cochlea. Brownell later made a major advance when he discovered that the ear has a mechanism for sound amplification, via outer hair cell electromotility. Images Figure 1 Figure 2 PMID:15369636

  17. Inner ear symptoms and disease: Pathophysiological understanding and therapeutic options

    PubMed Central

    Ciuman, Raphael R.

    2013-01-01

    In recent years, huge advances have taken place in understanding of inner ear pathophysiology causing sensorineural hearing loss, tinnitus, and vertigo. Advances in understanding comprise biochemical and physiological research of stimulus perception and conduction, inner ear homeostasis, and hereditary diseases with underlying genetics. This review describes and tabulates the various causes of inner ear disease and defines inner ear and non-inner ear causes of hearing loss, tinnitus, and vertigo. The aim of this review was to comprehensively breakdown this field of otorhinolaryngology for specialists and non-specialists and to discuss current therapeutic options in distinct diseases and promising research for future therapies, especially pharmaceutic, genetic, or stem cell therapy. PMID:24362017

  18. Sequoia regulates cell fate decisions in the external sensory organs of adult Drosophila.

    PubMed

    Andrews, Hillary K; Giagtzoglou, Nikolaos; Yamamoto, Shinya; Schulze, Karen L; Bellen, Hugo J

    2009-06-01

    The adult Drosophila external sensory organ (ESO), comprising the hair, socket, neuron, sheath and glia cells, arises through the asymmetric division of sensory organ precursor cells (SOPs). In a mosaic screen designed to identify new components in ESO development, we isolated mutations in sequoia, which encodes a putative zinc-finger transcription factor that has previously been shown to have a role in dendritogenesis. Here, we show that adult clones mutant for seq exhibit a loss of hair cells and a gain of socket cells. We propose that the seq mutant phenotype arises, in part, owing to the loss of several crucial transcription factors known to be important in peripheral nervous system development such as D-Pax2, Prospero and Hamlet. Thus, Sequoia is a new upstream regulator of genes that orchestrates cell fate specification during development of the adult ESO lineage.

  19. Sequoia regulates cell fate decisions in the external sensory organs of adult Drosophila

    PubMed Central

    Andrews, Hillary K; Giagtzoglou, Nikolaos; Yamamoto, Shinya; Schulze, Karen L; Bellen, Hugo J

    2009-01-01

    The adult Drosophila external sensory organ (ESO), comprising the hair, socket, neuron, sheath and glia cells, arises through the asymmetric division of sensory organ precursor cells (SOPs). In a mosaic screen designed to identify new components in ESO development, we isolated mutations in sequoia, which encodes a putative zinc-finger transcription factor that has previously been shown to have a role in dendritogenesis. Here, we show that adult clones mutant for seq exhibit a loss of hair cells and a gain of socket cells. We propose that the seq mutant phenotype arises, in part, owing to the loss of several crucial transcription factors known to be important in peripheral nervous system development such as D-Pax2, Prospero and Hamlet. Thus, Sequoia is a new upstream regulator of genes that orchestrates cell fate specification during development of the adult ESO lineage. PMID:19444309

  20. Evolutionary diversification of secondary mechanoreceptor cells in tunicata.

    PubMed

    Rigon, Francesca; Stach, Thomas; Caicci, Federico; Gasparini, Fabio; Burighel, Paolo; Manni, Lucia

    2013-06-04

    Hair cells are vertebrate secondary sensory cells located in the ear and in the lateral line organ. Until recently, these cells were considered to be mechanoreceptors exclusively found in vertebrates that evolved within this group. Evidence of secondary mechanoreceptors in some tunicates, the proposed sister group of vertebrates, has recently led to the hypothesis that vertebrate and tunicate secondary sensory cells share a common origin. Secondary sensory cells were described in detail in two tunicate groups, ascidians and thaliaceans, in which they constitute an oral sensory structure called the coronal organ. Among thaliaceans, the organ is absent in salps and it has been hypothesised that this condition is due to a different feeding system adopted by this group of animals. No information is available as to whether a comparable structure exists in the third group of tunicates, the appendicularians, although different sensory structures are known to be present in these animals. We studied the detailed morphology of appendicularian oral mechanoreceptors. Using light and electron microscopy we could demonstrate that the mechanosensory organ called the circumoral ring is composed of secondary sensory cells. We described the ultrastructure of the circumoral organ in two appendicularian species, Oikopleura dioica and Oikopleura albicans, and thus taxonomically completed the data collection of tunicate secondary sensory cells. To understand the evolution of secondary sensory cells in tunicates, we performed a cladistic analysis using morphological data. We constructed a matrix consisting of 19 characters derived from detailed ultrastructural studies in 16 tunicate species and used a cephalochordate and three vertebrate species as outgroups. Our study clearly shows that the circumoral ring is the appendicularian homologue of the coronal organ of other tunicate taxa. The cladistic analysis enabled us to reconstruct the features of the putative ancestral hair cell in

  1. Genetic analysis of vertebrate sensory hair cell mechanosensation: the zebrafish circler mutants.

    PubMed

    Nicolson, T; Rüsch, A; Friedrich, R W; Granato, M; Ruppersberg, J P; Nüsslein-Volhard, C

    1998-02-01

    The molecular basis of sensory hair cell mechanotransduction is largely unknown. In order to identify genes that are essential for mechanosensory hair cell function, we characterized a group of recently isolated zebrafish motility mutants. These mutants are defective in balance and swim in circles but have no obvious morphological defects. We examined the mutants using calcium imaging of acoustic-vibrational and tactile escape responses, high resolution microscopy of sensory neuroepithelia in live larvae, and recordings of extracellular hair cell potentials (microphonics). Based on the analyses, we have identified several classes of genes. Mutations in sputnik and mariner affect hair bundle integrity. Mutant astronaut and cosmonaut hair cells have relatively normal microphonics and thus appear to affect events downstream of mechanotransduction. Mutant orbiter, mercury, and gemini larvae have normal hair cell morphology and yet do not respond to acoustic-vibrational stimuli. The microphonics of lateral line hair cells of orbiter, mercury, and gemini larvae are absent or strongly reduced. Therefore, these genes may encode components of the transduction apparatus.

  2. Microbiomes of the normal middle ear and ears with chronic otitis media.

    PubMed

    Minami, Shujiro B; Mutai, Hideki; Suzuki, Tomoko; Horii, Arata; Oishi, Naoki; Wasano, Koichiro; Katsura, Motoyasu; Tanaka, Fujinobu; Takiguchi, Tetsuya; Fujii, Masato; Kaga, Kimitaka

    2017-10-01

    The aim of this study was to profile and compare the middle ear microbiomes of human subjects with and without chronic otitis media. Prospective multicenter cohort study. All consecutive patients undergoing tympanoplasty surgery for chronic otitis media or ear surgery for conditions other than otitis media were recruited. Sterile swab samples were collected from the middle ear mucosa during surgery. The variable region 4 of the 16S rRNA gene in each sample were amplified using region-specific primers adapted for the Illumina MiSeq sequencer (Illumina, CA, USA)). The sequences were subjected to local blast and classified using Metagenome@KIN (World Fusion, Tokyo, Japan). In total, 155 participants were recruited from seven medical centers. Of these, 88 and 67 had chronic otitis media and normal middle ears, respectively. The most abundant bacterial phyla on the mucosal surfaces of the normal middle ears were Proteobacteria, followed by Actinobacteria, Firmicutes, and Bacteroidetes. The children and adults with normal middle ears differed significantly in terms of middle ear microbiomes. Subjects with chronic otitis media without active inflammation (dry ear) had similar middle ear microbiomes as the normal middle ears group. Subjects with chronic otitis media with active inflammation (wet ear) had a lower prevalence of Proteobacteria and a higher prevalence of Firmicutes than the normal middle ears. The human middle ear is inhabited by more diverse microbial communities than was previously thought. Alteration of the middle ear microbiome may contribute to the pathogenesis of chronic otitis media with active inflammation. 2b. Laryngoscope, 127:E371-E377, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  3. Ear asymmetries in middle-ear, cochlear, and brainstem responses in human infants

    PubMed Central

    Keefe, Douglas H.; Gorga, Michael P.; Jesteadt, Walt; Smith, Lynette M.

    2008-01-01

    In 2004, Sininger and Cone-Wesson examined asymmetries in the signal-to-noise ratio (SNR) of otoacoustic emissions (OAE) in infants, reporting that distortion-product (DP)OAE SNR was larger in the left ear, whereas transient-evoked (TE)OAE SNR was larger in the right. They proposed that cochlear and brainstem asymmetries facilitate development of brain-hemispheric specialization for sound processing. Similarly, in 2006 Sininger and Cone-Wesson described ear asymmetries mainly favoring the right ear in infant auditory brainstem responses (ABRs). The present study analyzed 2640 infant responses to further explore these effects. Ear differences in OAE SNR, signal, and noise were evaluated separately and across frequencies (1.5, 2, 3, and 4 kHz), and ABR asymmetries were compared with cochlear asymmetries. Analyses of ear-canal reflectance and admittance showed that asymmetries in middle-ear functioning did not explain cochlear and brainstem asymmetries. Current results are consistent with earlier studies showing right-ear dominance for TEOAE and ABR. Noise levels were higher in the right ear for OAEs and ABRs, causing ear asymmetries in SNR to differ from those in signal level. No left-ear dominance for DPOAE signal was observed. These results do not support a theory that ear asymmetries in cochlear processing mimic hemispheric brain specialization for auditory processing. PMID:18345839

  4. Generation of sensory hair cells by genetic programming with a combination of transcription factors.

    PubMed

    Costa, Aida; Sanchez-Guardado, Luis; Juniat, Stephanie; Gale, Jonathan E; Daudet, Nicolas; Henrique, Domingos

    2015-06-01

    Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. Elucidation of the transcriptional networks regulating HC fate determination and differentiation is crucial not only to understand inner ear development but also to improve cell replacement therapies for hearing disorders. Here, we show that combined expression of the transcription factors Gfi1, Pou4f3 and Atoh1 can induce direct programming towards HC fate, both during in vitro mouse embryonic stem cell differentiation and following ectopic expression in chick embryonic otic epithelium. Induced HCs (iHCs) express numerous HC-specific markers and exhibit polarized membrane protrusions reminiscent of stereociliary bundles. Transcriptome profiling confirms the progressive establishment of a HC-specific gene signature during in vitro iHC programming. Overall, this work provides a novel approach to achieve robust and highly efficient HC production in vitro, which could be used as a model to study HC development and to drive inner ear HC regeneration. © 2015. Published by The Company of Biologists Ltd.

  5. 3D finite element model of the chinchilla ear for characterizing middle ear functions

    PubMed Central

    Wang, Xuelin; Gan, Rong Z.

    2016-01-01

    Chinchilla is a commonly used animal model for research of sound transmission through the ear. Experimental measurements of the middle ear transfer function in chinchillas have shown that the middle ear cavity greatly affects the tympanic membrane (TM) and stapes footplate (FP) displacements. However, there is no finite element (FE) model of the chinchilla ear available in the literature to characterize the middle ear functions with the anatomical features of the chinchilla ear. This paper reports a recently completed 3D FE model of the chinchilla ear based on X-ray micro-computed tomography images of a chinchilla bulla. The model consisted of the ear canal, TM, middle ear ossicles and suspensory ligaments, and the middle ear cavity. Two boundary conditions of the middle ear cavity wall were simulated in the model as the rigid structure and the partially flexible surface, and the acoustic-mechanical coupled analysis was conducted with these two conditions to characterize the middle ear function. The model results were compared with experimental measurements reported in the literature including the TM and FP displacements and the middle ear input admittance in chinchilla ear. An application of this model was presented to identify the acoustic role of the middle ear septa - a unique feature of chinchilla middle ear cavity. This study provides the first 3D FE model of the chinchilla ear for characterizing the middle ear functions through the acoustic-mechanical coupled FE analysis. PMID:26785845

  6. Assessment of Masses of the External Ear With Diffusion-Weighted MR Imaging.

    PubMed

    Razek, Ahmed Abdel Khalek Abdel

    2018-02-01

    To assess masses of the external ear with diffusion-weighted MR imaging. Retrospective analysis of 43 consecutive patients with soft tissue mass of the external ear. They underwent single shot diffusion-weighted MR imaging of the ear. The apparent diffusion coefficient (ADC) value of the mass of the external ear was calculated. The final diagnosis was performed by biopsy. The ADC value correlated with the biopsy results. The mean ADC value of malignancy (=27) of external ear (0.95 ± 0.19 × 10 mm/s) was significantly lower (p = 0.001) than that of benign (n = 16) lesions (1.49 ± 0.08 × 10 mm/s). The cutoff ADC used for differentiation of malignancy from benign lesions was 1.18 × 10 mm/s with an area under the curve of 0.959, an accuracy of 93%, a sensitivity of 92%, and specificity of 93%. There was a significant difference in the ADC of well and moderately differentiated malignancy versus poorly and undifferentiated squamous cell carcinoma (p = 0.001), and stages I and II versus stages III and IV (p = 0.04) of squamous cell carcinoma. ADC value is a non-invasive promising imaging parameter that can be used for differentiation of malignancy of the external ear from benign lesions, and grading and staging of squamous cell carcinoma of the external ear.

  7. Whole-Mount Adult Ear Skin Imaging Reveals Defective Neuro-Vascular Branching Morphogenesis in Obese and Type 2 Diabetic Mouse Models.

    PubMed

    Yamazaki, Tomoko; Li, Wenling; Yang, Ling; Li, Ping; Cao, Haiming; Motegi, Sei-Ichiro; Udey, Mark C; Bernhard, Elise; Nakamura, Takahisa; Mukouyama, Yoh-Suke

    2018-01-11

    Obesity and type 2 diabetes are frequently associated with peripheral neuropathy. Though there are multiple methods for diagnosis and analysis of morphological changes of peripheral nerves and blood vessels, three-dimensional high-resolution imaging is necessary to appreciate the pathogenesis with an anatomically recognizable branching morphogenesis and patterning. Here we established a novel technique for whole-mount imaging of adult mouse ear skin to visualize branching morphogenesis and patterning of peripheral nerves and blood vessels. Whole-mount immunostaining of adult mouse ear skin showed that peripheral sensory and sympathetic nerves align with large-diameter blood vessels. Diet-induced obesity (DIO) mice exhibit defective vascular smooth muscle cells (VSMCs) coverage, while there is no significant change in the amount of peripheral nerves. The leptin receptor-deficient db/db mice, a severe obese and type 2 diabetic mouse model, exhibit defective VSMC coverage and a large increase in the amount of smaller-diameter nerve bundles with myelin sheath and unmyelinated nerve fibers. Interestingly, an increase in the amount of myeloid immune cells was observed in the DIO but not db/db mouse skin. These data suggest that our whole-mount imaging method enables us to investigate the neuro-vascular and neuro-immune phenotypes in the animal models of obesity and diabetes.

  8. Middle ear application of a sodium hyaluronate gel loaded with neomycin in a Guinea pig model.

    PubMed

    Saber, Amanj; Laurell, Göran; Bramer, Tobias; Edsman, Katarina; Engmér, Cecilia; Ulfendahl, Mats

    2009-02-01

    Establishing methods for topical administration of drugs to the inner ear have great clinical relevance and potential even in a relatively short perspective. To evaluate the efficacy of sodium hyaluronate (HYA) as a vehicle for drugs that could be used for treatment of inner ear disorders. The cochlear hair cell loss and round window membrane (RWM) morphology were investigated after topical application of neomycin and HYA into the middle ear. Sixty-five albino guinea pigs were used and divided into groups depending on the type of the treatment. Neomycin was chosen as tracer for drug release and pharmacodynamic effect. HYA loaded with 3 different concentrations of neomycin was injected to the middle ear cavity of guinea pigs. Phalloidin stained surface preparations of the organ of Corti were used to estimate hair cell loss induced by neomycin. The thickness of the midportion of the RWM was measured and compared with that of controls using light and electron microscopy. All animal procedures were pe rformed in accordance with the ethical standards of Karolinska Institutet. Neomycin induced a considerable hair cell loss in guinea pigs receiving a middle ear injection of HYA loaded with the drug, demonstrating that neomycin was released from the gel and delivered to the inner ear. The resulting hair cell loss showed a clear dose-dependence. Only small differences in hair cell loss were noted between animals receiving neomycin solution and animals exposed to neomycin in HYA suggesting that the vehicle neither facilitated nor hindered drug transport between the middle ear cavity and the inner ear. One week after topical application, the thickness of the RWM had increased and was dependent upon the concentration of neomycin administered to the middle ear. At 4 weeks the thickness of the RWM had returned to normal. HYA is a safe vehicle for drugs aimed to pass into the inner ear through the RWM. Neomycin was released from HYA and transported into the inner ear as evidenced

  9. Concerted action of two dlx paralogs in sensory placode formation.

    PubMed

    Solomon, Keely S; Fritz, Andreas

    2002-07-01

    Sensory placodes are ectodermal thickenings that give rise to elements of the vertebrate cranial sensory nervous system, including the inner ear and nose. Although mutations have been described in humans, mice and zebrafish that perturb ear and nose development, no mutation is known to prevent sensory placode formation. Thus, it has been postulated that a functional redundancy exists in the genetic mechanisms that govern sensory placode development. We describe a zebrafish deletion mutation, b380, which results in a lack of both otic and olfactory placodes. The b380 deletion removes several known genes and expressed sequence tags, including dlx3 and dlx7, two transcription factors that share a homoeobox domain similar in sequence to the Drosophila Distal-less gene. dlx3 and dlx7 are expressed in an overlapping pattern in the regions that produce the otic and olfactory placodes in zebrafish. We present evidence suggesting that it is specifically the removal of these two genes that leads to the otic and olfactory phenotype of b380 mutants. Using morpholinos, antisense oligonucleotides that effectively block translation of target genes, we find that functional reduction of both dlx genes contributes to placode loss. Expression patterns of the otic marker pax2.1, olfactory marker anxV and eya1, a marker of both placodes, in morpholino-injected embryos recapitulate the reduced expression of these genes seen in b380 mutants. We also examine expression of dlx3 and dlx7 in the morpholino-injected embryos and present evidence for existence of auto- and cross-regulatory control of expression among these genes. We demonstrate that dlx3 is necessary and sufficient for proper otic and olfactory placode development. However, our results indicate that dlx3 and dlx7 act in concert and their importance in placode formation is only revealed by inactivating both paralogs.

  10. A historical to present-day account of efforts to answer the question, “What puts the brakes on mammalian hair cell regeneration?”

    PubMed Central

    Burns, Joseph C.; Corwin, Jeffrey T.

    2013-01-01

    Hearing and balance deficits often affect humans and other mammals permanently, because their ears stop producing hair cells within a few days after birth. But production occurs throughout life in the ears of sharks, bony fish, amphibians, reptiles, and birds allowing them to replace lost hair cells and quickly recover after temporarily experiencing the kinds of sensory deficits that are irreversible for mammals. Since the mid 1970's, researchers have been asking what puts the brakes on hair cell regeneration in mammals? Here we evaluate the headway that has been made and assess current evidence for various alternative mechanistic hypotheses that have been proposed to account for the limits to hair cell regeneration in mammals. PMID:23333259

  11. Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo

    NASA Technical Reports Server (NTRS)

    Matsui, Jonathan I.; Haque, Asim; Huss, David; Messana, Elizabeth P.; Alosi, Julie A.; Roberson, David W.; Cotanche, Douglas A.; Dickman, J. David; Warchol, Mark E.

    2003-01-01

    The sensory hair cells of the inner ear undergo apoptosis after acoustic trauma or aminoglycoside antibiotic treatment, causing permanent auditory and vestibular deficits in humans. Previous studies have demonstrated a role for caspase activation in hair cell death and ototoxic injury that can be reduced by concurrent treatment with caspase inhibitors in vitro. In this study, we examined the protective effects of caspase inhibition on hair cell death in vivo after systemic injections of aminoglycosides. In one series of experiments, chickens were implanted with osmotic pumps that administrated the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (zVAD) into inner ear fluids. One day after the surgery, the animals received a 5 d course of treatment with streptomycin, a vestibulotoxic aminoglycoside. Direct infusion of zVAD into the vestibule significantly increased hair cell survival after streptomycin treatment. A second series of experiments determined whether rescued hair cells could function as sensory receptors. Animals treated with streptomycin displayed vestibular system impairment as measured by a greatly reduced vestibulo-ocular response (VOR). In contrast, animals that received concurrent systemic administration of zVAD with streptomycin had both significantly greater hair cell survival and significantly increased VOR responses, as compared with animals treated with streptomycin alone. These findings suggest that inhibiting the activation of caspases promotes the survival of hair cells and protects against vestibular function deficits after aminoglycoside treatment.

  12. Regeneration of Sensory Hair Cells Requires Localized Interactions between the Notch and Wnt Pathways.

    PubMed

    Romero-Carvajal, Andrés; Navajas Acedo, Joaquín; Jiang, Linjia; Kozlovskaja-Gumbrienė, Agnė; Alexander, Richard; Li, Hua; Piotrowski, Tatjana

    2015-08-10

    In vertebrates, mechano-electrical transduction of sound is accomplished by sensory hair cells. Whereas mammalian hair cells are not replaced when lost, in fish they constantly renew and regenerate after injury. In vivo tracking and cell fate analyses of all dividing cells during lateral line hair cell regeneration revealed that support and hair cell progenitors localize to distinct tissue compartments. Importantly, we find that the balance between self-renewal and differentiation in these compartments is controlled by spatially restricted Notch signaling and its inhibition of Wnt-induced proliferation. The ability to simultaneously study and manipulate individual cell behaviors and multiple pathways in vivo transforms the lateral line into a powerful paradigm to mechanistically dissect sensory organ regeneration. The striking similarities to other vertebrate stem cell compartments uniquely place zebrafish to help elucidate why mammals possess such low capacity to regenerate hair cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Requirements for FGF3 and FGF10 during inner ear formation.

    PubMed

    Alvarez, Yolanda; Alonso, Maria Teresa; Vendrell, Victor; Zelarayan, Laura Cecilia; Chamero, Pablo; Theil, Thomas; Bösl, Michael R; Kato, Shigeaki; Maconochie, Mark; Riethmacher, Dieter; Schimmang, Thomas

    2003-12-01

    Members of the fibroblast growth factor (FGF) gene family control formation of the body plan and organogenesis in vertebrates. FGF3 is expressed in the developing hindbrain and has been shown to be involved in inner ear development of different vertebrate species, including zebrafish, Xenopus, chick and mouse. In the mouse, insertion of a neomycin resistance gene into the Fgf3 gene via homologous recombination results in severe developmental defects during differentiation of the otic vesicle. We have addressed the precise roles of FGF3 and other FGF family members during formation of the murine inner ear using both loss- and gain-of-function experiments. We generated a new mutant allele lacking the entire FGF3-coding region but surprisingly found no evidence for severe defects either during inner ear development or in the mature sensory organ, suggesting the functional involvement of other FGF family members during its formation. Ectopic expression of FGF10 in the developing hindbrain of transgenic mice leads to the formation of ectopic vesicles, expressing some otic marker genes and thus indicating a role for FGF10 during otic vesicle formation. Expression analysis of FGF10 during mouse embryogenesis reveals a highly dynamic pattern of expression in the developing hindbrain, partially overlapping with FGF3 expression and coinciding with formation of the inner ear. However, FGF10 mutant mice have been reported to display only mild defects during inner ear differentiation. We thus created double mutant mice for FGF3 and FGF10, which form severely reduced otic vesicles, suggesting redundant roles of these FGFs, acting in combination as neural signals for otic vesicle formation.

  14. Some Remarks on Imaging of the Inner Ear: Options and Limitations.

    PubMed

    Giesemann, A; Hofmann, E

    2015-10-01

    The temporal bone has a highly complex anatomical structure, in which the sensory organs of the cochlea and the vestibular system are contained within a small space together with the sound-conducting system of the middle ear. Detailed imaging is thus required in this anatomical area. There are a great many clinical aims for which the highest-possible spatial resolution is required. These include the localization of cerebrospinal fluid fistulas, the detection of malformations of the middle and inner ear and the vestibulocochlear nerve, an aberrant course of the facial nerve and anomalies of the arterial and venous structures, the confirmation of dehiscence of the semicircular canals and finally, the verification of endolymphatic hydrops in cases of Ménière's disease. However, the term 'high resolution' is very time dependent. Two milestones in this respect have been (in 1991) the 3D visualization of the inner ear by means of maximum-intensity projection (MIP) of a T2-weighted constructive interference in steady state (CISS) sequence of a 1.5-tesla magnetic resonance imaging (MRI) scanner (Tanioka et al., Radiology 178:141-144, 1991) and (in 1997) imaging of the vestibulocochlear nerve for the diagnosis of hypoplasia inside the internal auditory canal using the same sequence (Casselman et al., Radiology 202:773-781, 1997).The objective of this article is to highlight the options for, and the challenges of, contemporary imaging with regard to some clinical issues relating to the inner ear.

  15. Cilia distribution and polarity in the epithelial lining of the mouse middle ear cavity

    PubMed Central

    Luo, Wenwei; Yi, Hong; Taylor, Jeannette; Li, Jian-dong; Chi, Fanglu; Todd, N. Wendell; Lin, Xi; Ren, Dongdong; Chen, Ping

    2017-01-01

    The middle ear conducts sound to the cochlea for hearing. Otitis media (OM) is the most common illness in childhood. Moreover, chronic OM with effusion (COME) is the leading cause of conductive hearing loss. Clinically, COME is highly associated with Primary Ciliary Dyskinesia, implicating significant contributions of cilia dysfunction to COME. The understanding of middle ear cilia properties that are critical to OM susceptibility, however, is limited. Here, we confirmed the presence of a ciliated region near the Eustachian tube orifice at the ventral region of the middle ear cavity, consisting mostly of a lumen layer of multi-ciliated and a layer of Keratin-5-positive basal cells. We also found that the motile cilia are polarized coordinately and display a planar cell polarity. Surprisingly, we also found a region of multi-ciliated cells that line the posterior dorsal pole of the middle ear cavity which was previously thought to contain only non-ciliated cells. Our study provided a more complete understanding of cilia distribution and revealed for the first time coordinated polarity of cilia in the epithelium of the mammalian middle ear, thus illustrating novel structural features that are likely critical for middle ear functions and related to OM susceptibility. PMID:28358397

  16. Analysis of the Proteome of Hair-Cell Stereocilia by Mass Spectrometry

    PubMed Central

    Krey, Jocelyn F.; Wilmarth, Philip A.; David, Larry L.; Barr-Gillespie, Peter G.

    2017-01-01

    Characterization of proteins that mediate mechanotransduction by hair cells, the sensory cells of the inner ear, is hampered by the scarcity of these cells and their sensory organelle, the hair bundle. Mass spectrometry, with its high sensitivity and identification precision, is the ideal method for determining which proteins are present in bundles and what proteins they interact with. We describe here the isolation of mouse hair bundles, as well as preparation of bundle-protein samples for mass spectrometry. We also describe protocols for data-dependent (shotgun) and parallel-reaction-monitoring (targeted) mass spectrometry that allow us to identify and quantify proteins of the hair bundle. These sensitive methods are particularly useful for comparing proteomes of wild-type and mice with deafness mutations affecting hair-bundle proteins. (120 words; maximum 250) PMID:28109437

  17. Swimmer's Ear (For Parents)

    MedlinePlus

    ... scratching the ear canal, vigorous ear cleaning with cotton swabs, or putting foreign objects like bobby pins ... Also, never put objects into kids' ears, including cotton-tipped swabs. How Is Swimmer's Ear Treated? Treatment ...

  18. ILDR1 null mice, a model of human deafness DFNB42, show structural aberrations of tricellular tight junctions and degeneration of auditory hair cells

    PubMed Central

    Morozko, Eva L.; Nishio, Ayako; Ingham, Neil J.; Chandra, Rashmi; Fitzgerald, Tracy; Martelletti, Elisa; Borck, Guntram; Wilson, Elizabeth; Riordan, Gavin P.; Wangemann, Philine; Forge, Andrew; Steel, Karen P.; Liddle, Rodger A.; Friedman, Thomas B.; Belyantseva, Inna A.

    2015-01-01

    In the mammalian inner ear, bicellular and tricellular tight junctions (tTJs) seal the paracellular space between epithelial cells. Tricellulin and immunoglobulin-like (Ig-like) domain containing receptor 1 (ILDR1, also referred to as angulin-2) localize to tTJs of the sensory and non-sensory epithelia in the organ of Corti and vestibular end organs. Recessive mutations of TRIC (DFNB49) encoding tricellulin and ILDR1 (DFNB42) cause human nonsyndromic deafness. However, the pathophysiology of DFNB42 deafness remains unknown. ILDR1 was recently reported to be a lipoprotein receptor mediating the secretion of the fat-stimulated cholecystokinin (CCK) hormone in the small intestine, while ILDR1 in EpH4 mouse mammary epithelial cells in vitro was shown to recruit tricellulin to tTJs. Here we show that two different mouse Ildr1 mutant alleles have early-onset severe deafness associated with a rapid degeneration of cochlear hair cells (HCs) but have a normal endocochlear potential. ILDR1 is not required for recruitment of tricellulin to tTJs in the cochlea in vivo; however, tricellulin becomes mislocalized in the inner ear sensory epithelia of ILDR1 null mice after the first postnatal week. As revealed by freeze-fracture electron microscopy, ILDR1 contributes to the ultrastructure of inner ear tTJs. Taken together, our data provide insight into the pathophysiology of human DFNB42 deafness and demonstrate that ILDR1 is crucial for normal hearing by maintaining the structural and functional integrity of tTJs, which are critical for the survival of auditory neurosensory HCs. PMID:25217574

  19. P2X antagonists inhibit styryl dye entry into hair cells.

    PubMed

    Crumling, M A; Tong, M; Aschenbach, K L; Liu, L Qian; Pipitone, C M; Duncan, R K

    2009-07-21

    The styryl pyridinium dyes, FM1-43 and AM1-43, are fluorescent molecules that can permeate the mechanotransduction channels of hair cells, the sensory receptors of the inner ear. When these dyes are applied to hair cells, they enter the cytoplasm rapidly, resulting in a readily detectable intracellular fluorescence that is often used as a molecular indication of mechanotransduction channel activity. However, such dyes can also permeate the ATP receptor, P2X(2). Therefore, we explored the contribution of P2X receptors to the loading of hair cells with AM1-43. The chick inner ear was found to express P2X receptors and to release ATP, similar to the inner ear of mammals, allowing for the endogenous stimulation of P2X receptors. The involvement of these receptors was evaluated pharmacologically, by exposing the sensory epithelium of the chick inner ear to 5 microM AM1-43 under different experimental conditions and measuring the fluorescence in hair cells after fixation of the tissue. Pre-exposure of the tissue to 5 mM EGTA for 15 min, which should eliminate most of the gating "tip links" of the mechanotransduction channels, deceased fluorescence by only 44%. In contrast, P2X receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid [PPADS], suramin, 2',3'-O-(2,4,6-trinitrophenyl) ATP [TNP-ATP], and d-tubocurarine) had greater effects on dye loading. PPADS, suramin, and TNP-ATP all decreased intracellular AM1-43 fluorescence in hair cells by at least 69% when applied at a concentration of 100 microM. The difference between d-tubocurarine-treated and control fluorescence was statistically insignificant when d-tubocurarine was applied at a concentration that blocks the mechanotransduction channel (200 microM). At a concentration that also blocks P2X(2) receptors (2 mM), d-tubocurarine decreased dye loading by 72%. From these experiments, it appears that AM1-43 can enter hair cells through endogenously activated P2X receptors. Thus, the contribution of P2X

  20. Induction of sensory neurons from neuroepithelial stem cells by the ISX9 small molecule

    PubMed Central

    Ali, Rouknuddin Qasim; Blomberg, Evelina; Falk, Anna; Ährlund-Richter, Lars; Ulfendahl, Mats

    2016-01-01

    Hearing impairment most often involves loss of sensory hair cells and auditory neurons. As this loss is permanent in humans, a cell therapy approach has been suggested to replace damaged cells. It is thus of interest to generate lineage restricted progenitor cells appropriate for cell based therapies. Human long-term self-renewing neuroepithelial stem (lt-NES) cell lines exhibit in vitro a developmental potency to differentiate into CNS neural lineages, and importantly lack this potency in vivo, i.e do not form teratomas. Small-molecules-driven differentiation is today an established route obtain specific cell derivatives from stem cells. In this study, we have investigated the effects of three small molecules SB431542, ISX9 and Metformin to direct differentiation of lt-NES cells into sensory neurons. Exposure of lt-NES cells to Metformin or SB431542 did not induce any marked induction of markers for sensory neurons. However, a four days exposure to the ISX9 small molecule resulted in reduced expression of NeuroD1 mRNA as well as enhanced mRNA levels of GATA3, a marker and important player in auditory neuron specification and development. Subsequent culture in the presence of the neurotrophic factors BDNF and NT3 for another seven days yielded a further increase of mRNA expression for GATA3. This regimen resulted in a frequency of up to 25-30% of cells staining positive for Brn3a/Tuj1. We conclude that an approach with ISX9 small molecule induction of lt-NES cells into auditory like neurons may thus be an attractive route for obtaining safe cell replacement therapy of sensorineural hearing loss. PMID:27335699

  1. Expansion method in secondary total ear reconstruction for undesirable reconstructed ear.

    PubMed

    Liu, Tun; Hu, Jintian; Zhou, Xu; Zhang, Qingguo

    2014-09-01

    Ear reconstruction by autologous costal cartilage grafting is the most widely applied technique with fewer complications. However, undesirable ear reconstruction brings more problems to plastic surgeons. Some authors resort to free flap or osseointegration technique with prosthetic ear. In this article, we introduce a secondary total ear reconstruction with expanded skin flap method. From July 2010 to April 2012, 7 cases of undesirable ear reconstruction were repaired by tissue expansion method. Procedures including removal of previous cartilage framework, soft tissue expander insertion, and second stage of cartilage framework insertion were performed to each case regarding their local conditions. The follow-up time ranged from 6 months to 2.5 years. All of the cases recovered well with good 3-dimensional forms, symmetrical auriculocephalic angle, and stable fixation. All these evidence showed that this novel expansion method is safe, stable, and less traumatic for secondary total ear reconstruction. With sufficient expanded skin flap and refabricated cartilage framework, lifelike appearance of reconstructed ear could be acquired without causing additional injury.

  2. A historical to present-day account of efforts to answer the question: "what puts the brakes on mammalian hair cell regeneration?".

    PubMed

    Burns, Joseph C; Corwin, Jeffrey T

    2013-03-01

    Hearing and balance deficits often affect humans and other mammals permanently, because their ears stop producing hair cells within a few days after birth. But production occurs throughout life in the ears of sharks, bony fish, amphibians, reptiles, and birds allowing them to replace lost hair cells and quickly recover after temporarily experiencing the kinds of sensory deficits that are irreversible for mammals. Since the mid 1970s, researchers have been asking what puts the brakes on hair cell regeneration in mammals. Here we evaluate the headway that has been made and assess current evidence for alternative mechanistic hypotheses that have been proposed to account for the limits to hair cell regeneration in mammals. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Espin cytoskeletal proteins in the sensory cells of rodent taste buds

    PubMed Central

    Sekerková, Gabriella; Freeman, David; Mugnaini, Enrico; Bartles, James R.

    2010-01-01

    Espins are multifunctional actin-bundling proteins that are highly enriched in the microvilli of certain chemosensory and mechanosensory cells, where they are believed to regulate the integrity and/or dimensions of the parallel-actin-bundle cytoskeletal scaffold. We have determined that, in rats and mice, affinity purified espin antibody intensely labels the lingual and palatal taste buds of the oral cavity and taste buds in the pharyngo-laryngeal region. Intense immunolabeling was observed in the apical, microvillar region of taste buds, while the level of cytoplasmic labeling in taste bud cells was considerably lower. Taste bud cells contain tightly packed collections of sensory cells (light, or type II plus type III) and supporting cells (dark, or type I), which can be distinguished by microscopic features and cell type-specific markers. On the basis of results obtained using an antigen-retrieval method in conjunction with double immunofluorescence for espin and sensory taste cell-specific markers, we propose that espins are expressed predominantly in the sensory cells of rat circumvallate taste buds. In confocal images, we counted 21.5±0.3 espin-positive cells/taste bud, in agreement with a previous report showing 20.7±1.3 light cells/taste bud when counted at the ultrastructural level. The espin antibody labeled spindle-shaped cells with round nuclei and showed 100% colocalization with cell-specific markers recognizing all type II [inositol 1,4,5-trisphosphate receptor type III (IP3R3),α-gustducin, protein-specific gene product 9.5 (PGP9.5)] and a subpopulation of type III (IP3R3, PGP9.5) taste cells. On average, 72%, 50%, and 32% of the espin-positive taste cells were labeled with antibodies to IP3R3, α-gustducin, and PGP9.5, respectively. Upon sectional analysis, the taste buds of rat circumvallate papillae commonly revealed a multi-tiered, espin-positive apical cytoskeletal apparatus. One espin-positive zone, a collection of ~3 μm-long microvilli

  4. Biocompatibility of Liposome Nanocarriers in the Rat Inner Ear After Intratympanic Administration

    NASA Astrophysics Data System (ADS)

    Zou, Jing; Feng, Hao; Sood, Rohit; Kinnunen, Paavo K. J.; Pyykko, Ilmari

    2017-05-01

    Liposome nanocarriers (LPNs) are potentially the future of inner ear therapy due to their high drug loading capacity and efficient uptake in the inner ear after a minimally invasive intratympanic administration. However, information on the biocompatibility of LPNs in the inner ear is lacking. The aim of the present study is to document the biocompatibility of LPNs in the inner ear after intratympanic delivery. LPNs with or without gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) were delivered to the rats through transtympanic injection. The distribution of the Gd-DOTA-containing LPNs in the middle and inner ear was tracked in vivo using MRI. The function of the middle and inner ear barriers was evaluated using gadolinium-enhanced MRI. The auditory function was measured using auditory brainstem response (ABR). The potential inflammatory response was investigated by analyzing glycosaminoglycan and hyaluronic acid secretion and CD44 and TLR2 expression in the inner ear. The potential apoptosis was analyzed using terminal transferase (TdT) to label the free 3'OH breaks in the DNA strands of apoptotic cells with TMR-dUTP (TUNEL staining). As a result, LPNs entered the inner ear efficiently after transtympanic injection. The transtympanic injection of LPNs with or without Gd-DOTA neither disrupted the function of the middle and inner ear barriers nor caused hearing impairment in rats. The critical inflammatory biological markers in the inner ear, including glycosaminoglycan and hyaluronic acid secretion and CD44 and TLR2 expression, were not influenced by the administration of LPNs. There was no significant cell death associated with the administration of LPNs. The transtympanic injection of LPNs is safe for the inner ear, and LPNs may be applied as a drug delivery matrix in the clinical therapy of sensorineural hearing loss.

  5. Middle Ear Infections and Ear Tube Surgery (For Parents)

    MedlinePlus

    ... Infection? Swimmer's Ear Perforated Eardrum Hearing Impairment Swimmer's Ear (External ... All information on KidsHealth® is for educational purposes only. For specific medical advice, diagnoses, and treatment, ...

  6. Generation and characterization of Atoh1-Cre knock-in mouse line

    PubMed Central

    Yang, Hua; Xie, Xiaoling; Deng, Min; Chen, Xiaowei; Gan, Lin

    2010-01-01

    Summary Atoh1 encodes a basic helix-loop-helix (bHLH) transcription factor required for the development of the inner ear sensory epithelia, the dorsal spinal cord, brainstem, cerebellum, and intestinal secretory cells. In this study to create a genetic tool for the research on gene function in the ear sensory organs, we generated an Atoh1-Cre knock-in mouse line by replacing the entire Atoh1 coding sequences with the Cre coding sequences. Atoh1Cre/+mice were viable, fertile, and displayed no visible defects whereas the Atoh1Cre/Cremice died perinatally. The spatiotemporal activities of Cre recombinase were examined by crossing Atoh1-Cre mice with the R26R-lacZ conditional reporter mice. Atoh1-Cre activities were detected in the developing inner ear, the hindbrain, the spinal cord, and the intestine. In the inner ear, Atoh1-Cre activities were confined to the sensory organs in which lacZ expression is detected in nearly all of the hair cells and in many supporting cells. Thus, Atoh1-Cre mouse line serves as a useful tool for the functional study of genes in the inner ear. In addition, our results demonstrate that Atoh1 is expressed in the common progenitors destined for both hair and supporting cells. PMID:20533400

  7. Surgical correction of constricted ear combined with Stahl's ear.

    PubMed

    Bi, Ye; Lin, Lin; Yang, Qinhua; Pan, Bo; Zhao, Yanyong; He, Leren; Jiang, Haiyue

    2015-07-01

    Constricted ear combined with Stahl's ear is a rare ear deformity, which is a kind of complex congenital auricular deformity. From 1 January 2007 to 1 January 2014, 19 patients with constricted ear combined with Stahl's ear (Spock ear) were enrolled in this study, most of which were unilaterally deformed. To correct the deformity, a double Z-shaped skin incision was made on the posterior side of the auricle, with the entire layer of cartilage cut parallel to the helix traversing the third crus to form a fan-shaped cartilage flap. The superior crura of the antihelix were shaped by the folding cartilage rim. The cartilage of the abnormal third crus was made part of the new superior crura of antihelix, and the third crus was eliminated. The postoperative aesthetic assessment of the reshaped auricle was graded by both doctors and patients (or their parents). Out of the 19 patients, the number of satisfying cases of the symmetry, helix stretch, elimination of the third crus, the cranioauricular angle, and the substructure of the reshaped ears was 14 (nine excellent and five good), 16 (six excellent and 10 good), 17 (eight excellent and nine good), 15 (five excellent and 10 good), and 13 (two excellent and 11 good), respectively. With a maximum of a 90-month follow-up, no complication was observed. The results of the study suggested that this rare deformity could be corrected by appropriate surgical treatment, with a satisfied postoperative appearance. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  8. Elephant ear

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002867.htm Elephant ear poisoning To use the sharing features on this page, please enable JavaScript. Elephant ear plants are indoor or outdoor plants with ...

  9. Historical Aspects of Inner Ear Anatomy and Biology that Underlie the Design of Hearing and Balance Prosthetic Devices.

    PubMed

    Van De Water, Thomas R

    2012-11-01

    This review presents some of the major historical events that advanced the body of knowledge of the anatomy of the inner ear and its sensory receptors as well as the biology of these receptors that underlies the sensory functions of hearing and balance. This knowledge base of the inner ear's structure/function has been an essential factor for the design and construction of prosthetic devices to aid patients with deficits in their senses of hearing and balance. Prosthetic devices are now available for severely hearing impaired and deaf patients to restore hearing and are known as cochlear implants and auditory brain stem implants. A prosthetic device for patients with balance disorders is being perfected and is in an animal model testing phase with another prosthetic device for controlling intractable dizziness in Meniere's patients currently being evaluated in clinical testing. None of this would have been possible without the pioneering studies and discoveries of the investigators mentioned in this review and with the work of many other talented investigators to numerous to be covered in this review. Copyright © 2012 Wiley Periodicals, Inc.

  10. Airplane Ear

    MedlinePlus

    ... to severe hearing loss Ringing in your ear (tinnitus) Spinning sensation (vertigo) Vomiting resulting from vertigo Bleeding ... complications may include: Permanent hearing loss Ongoing (chronic) tinnitus Prevention Follow these tips to avoid airplane ear: ...

  11. Your Ears

    MedlinePlus

    ... Protect your hearing by wearing earplugs at loud music concerts and around noisy machinery, like in wood ... More on this topic for: Kids Can Loud Music Hurt My Ears? What Is an Ear Infection? ...

  12. Fgf8 and Fgf3 are required for zebrafish ear placode induction, maintenance and inner ear patterning.

    PubMed

    Léger, Sophie; Brand, Michael

    2002-11-01

    The vertebrate inner ear develops from initially 'simple' ectodermal placode and vesicle stages into the complex three-dimensional structure which is necessary for the senses of hearing and equilibrium. Although the main morphological events in vertebrate inner ear development are known, the genetic mechanisms controlling them are scarcely understood. Previous studies have suggested that the otic placode is induced by signals from the chordamesoderm and the hindbrain, notably by fibroblast growth factors (Fgfs) and Wnt proteins. Here we study the role of Fgf8 as a bona-fide hindbrain-derived signal that acts in conjunction with Fgf3 during placode induction, maintenance and otic vesicle patterning. Acerebellar (ace) is a mutant in the fgf8 gene that results in a non-functional Fgf8 product. Homozygous mutants for acerebellar (ace) have smaller ears that typically have only one otolith, abnormal semi-circular canals, and behavioral defects. Using gene expression markers for the otic placode, we find that ace/fgf8 and Fgf-signaling are required for normal otic placode formation and maintenance. Conversely, misexpression of fgf8 or Fgf8-coated beads implanted into the vicinity of the otic placode can increase ear size and marker gene expression, although competence to respond to the induction appears restricted. Cell transplantation experiments and expression analysis suggest that Fgf8 is required in the hindbrain in the rhombomere 4-6 area to restore normal placode development in ace mutants, in close neighbourhood to the forming placode, but not in mesodermal tissues. Fgf3 and Fgf8 are expressed in hindbrain rhombomere 4 during the stages that are critical for placode induction. Joint inactivation of Fgf3 and Fgf8 by mutation or antisense-morpholino injection causes failure of placode formation and results in ear-less embryos, mimicking the phenotype we observe after pharmacological inhibition of Fgf-signaling. Fgf8 and Fgf3 together therefore act during induction

  13. RNA analysis of inner ear cells from formalin fixed paraffin embedded (FFPE) archival human temporal bone section using laser microdissection--a technical report.

    PubMed

    Kimura, Yurika; Kubo, Sachiho; Koda, Hiroko; Shigemoto, Kazuhiro; Sawabe, Motoji; Kitamura, Ken

    2013-08-01

    Molecular analysis using archival human inner ear specimens is challenging because of the anatomical complexity, long-term fixation, and decalcification. However, this method may provide great benefit for elucidation of otological diseases. Here, we extracted mRNA for RT-PCR from tissues dissected from archival FFPE human inner ears by laser microdissection. Three human temporal bones obtained at autopsy were fixed in formalin, decalcified by EDTA, and embedded in paraffin. The samples were isolated into spiral ligaments, outer hair cells, spiral ganglion cells, and stria vascularis by laser microdissection. RNA was extracted and heat-treated in 10 mM citrate buffer to remove the formalin-derived modification. To identify the sites where COCH and SLC26A5 mRNA were expressed, semi-nested RT-PCR was performed. We also examined how long COCH mRNA could be amplified by semi-nested RT-PCR in archival temporal bone. COCH was expressed in the spiral ligament and stria vascularis. However, SLC26A5 was expressed only in outer hair cells. The maximum base length of COCH mRNA amplified by RT-PCR was 98 bp in 1 case and 123 bp in 2 cases. We detected COCH and SLC26A5 mRNA in specific structures and cells of the inner ear from archival human temporal bone. Our innovative method using laser microdissection and semi-nested RT-PCR should advance future RNA study of human inner ear diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. In situ tissue engineering with synthetic self-assembling peptide nanofiber scaffolds, PuraMatrix, for mucosal regeneration in the rat middle-ear

    PubMed Central

    Akiyama, Naotaro; Yamamoto-Fukuda, Tomomi; Takahashi, Haruo; Koji, Takehiko

    2013-01-01

    Middle-ear mucosa maintains middle-ear pressure. However, the majority of surgical cases exhibit inadequate middle-ear mucosal regeneration, and mucosal transplantation is necessary in such cases. The aim of the present study was to assess the feasibility of transplantation of isolated mucosal cells encapsulated within synthetic self-assembling peptide nanofiber scaffolds using PuraMatrix, which has been successfully used as scaffolding in tissue engineering, for the repair of damaged middle-ear. Middle-ear bullae with mucosa were removed from Sprague Dawley (SD) transgenic rats, transfected with enhanced green fluorescent protein (EGFP) transgene and excised into small pieces, then cultured up to the third passage. After surgical elimination of middle-ear mucosa in SD recipient rats, donor cells were encapsulated within PuraMatrix and transplanted into these immunosuppressed rats. Primary cultured cells were positive for pancytokeratin but not for vimentin, and retained the character of middle-ear epithelial cells. A high proportion of EGFP-expressing cells were found in the recipient middle-ear after transplantation with PuraMatrix, but not without PuraMatrix. These cells retained normal morphology and function, as confirmed by histological examination, immunohistochemistry, and electron microscopy, and multiplied to form new epithelial and subepithelial layers together with basement membrane. The present study demonstrated the feasibility of transplantation of cultured middle-ear mucosal epithelial cells encapsulated within PuraMatrix for regeneration of surgically eliminated mucosa of the middle-ear in SD rats. PMID:23926427

  15. In situ tissue engineering with synthetic self-assembling peptide nanofiber scaffolds, PuraMatrix, for mucosal regeneration in the rat middle-ear.

    PubMed

    Akiyama, Naotaro; Yamamoto-Fukuda, Tomomi; Takahashi, Haruo; Koji, Takehiko

    2013-01-01

    Middle-ear mucosa maintains middle-ear pressure. However, the majority of surgical cases exhibit inadequate middle-ear mucosal regeneration, and mucosal transplantation is necessary in such cases. The aim of the present study was to assess the feasibility of transplantation of isolated mucosal cells encapsulated within synthetic self-assembling peptide nanofiber scaffolds using PuraMatrix, which has been successfully used as scaffolding in tissue engineering, for the repair of damaged middle-ear. Middle-ear bullae with mucosa were removed from Sprague Dawley (SD) transgenic rats, transfected with enhanced green fluorescent protein (EGFP) transgene and excised into small pieces, then cultured up to the third passage. After surgical elimination of middle-ear mucosa in SD recipient rats, donor cells were encapsulated within PuraMatrix and transplanted into these immunosuppressed rats. Primary cultured cells were positive for pancytokeratin but not for vimentin, and retained the character of middle-ear epithelial cells. A high proportion of EGFP-expressing cells were found in the recipient middle-ear after transplantation with PuraMatrix, but not without PuraMatrix. These cells retained normal morphology and function, as confirmed by histological examination, immunohistochemistry, and electron microscopy, and multiplied to form new epithelial and subepithelial layers together with basement membrane. The present study demonstrated the feasibility of transplantation of cultured middle-ear mucosal epithelial cells encapsulated within PuraMatrix for regeneration of surgically eliminated mucosa of the middle-ear in SD rats.

  16. Supporting cells remove and replace sensory receptor hair cells in a balance organ of adult mice

    PubMed Central

    Bucks, Stephanie A; Cox, Brandon C; Vlosich, Brittany A; Manning, James P; Nguyen, Tot B; Stone, Jennifer S

    2017-01-01

    Vestibular hair cells in the inner ear encode head movements and mediate the sense of balance. These cells undergo cell death and replacement (turnover) throughout life in non-mammalian vertebrates. However, there is no definitive evidence that this process occurs in mammals. We used fate-mapping and other methods to demonstrate that utricular type II vestibular hair cells undergo turnover in adult mice under normal conditions. We found that supporting cells phagocytose both type I and II hair cells. Plp1-CreERT2-expressing supporting cells replace type II hair cells. Type I hair cells are not restored by Plp1-CreERT2-expressing supporting cells or by Atoh1-CreERTM-expressing type II hair cells. Destruction of hair cells causes supporting cells to generate 6 times as many type II hair cells compared to normal conditions. These findings expand our understanding of sensorineural plasticity in adult vestibular organs and further elucidate the roles that supporting cells serve during homeostasis and after injury. DOI: http://dx.doi.org/10.7554/eLife.18128.001 PMID:28263708

  17. Ear examination

    MedlinePlus

    ... ear anatomy Otoscopic exam of the ear References King EF, Couch ME. History, physical examination, and the ... commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer ...

  18. Expression of keratinocyte growth factor (KGF) and its receptor in a middle-ear cavity problem.

    PubMed

    Yamamoto-Fukuda, Tomomi; Takahashi, Haruo; Koji, Takehiko

    2012-01-01

    To investigate the pathogenesis of one of the most troublesome conditions following ear surgery, a middle-ear cavity problem. Keratinocyte growth factor (KGF) and its receptor (KGFR), the ratio of proliferating epithelial cells using Ki-67, and the extent of infiltration of B cells and T cells were examined immunohistochemically in 10 ears with a cavity problem, 70 ears with cholesteatoma and 8 ears with normal skin at the retroauricular incision. KGF was positive in 40% of cavity problem specimens, 37.5% of normal skin specimens, and was positive in 88% of cholesteatoma specimens (cavity problem vs. cholesteatoma, p=0.0004). The positive rate of KGFR in the cavity problem group (33.3%) was between those in cholesteatoma (60%) and normal skin (0%). In contrast to the cholesteatoma specimens, a significantly smaller number of Ki-67 labeling index (LI) was detected in the cavity problem specimens. B cell LI was significantly higher but T cell LI was significantly lower in the cavity problem specimens than in the cholesteatoma group. Our present study indicated that the discordance of paracrine action between stromal KGF and epithelial KGFR with a large number of infiltrating B cells may play an important role in the pathogenesis of a cavity problem. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Inner ear disorders.

    PubMed

    Smouha, Eric

    2013-01-01

    To present a framework for the diagnosis and treatment of inner ear disorders, with an emphasis on problems common to neuro-rehabilitation. Disorders of the inner ear can cause hearing loss, tinnitus, vertigo and imbalance. Hearing loss can be conductive, sensorineural, or mixed; conductive hearing loss arises from the ear canal or middle ear, while sensorineural hearing loss arises from the inner ear or auditory nerve. Vertigo is a hallucination of motion, and is the cardinal symptom of vestibular system disease. It should be differentiated from other causes of dizziness: gait imbalance, disequilibrium, lightheadedness (pre-syncope). Vertigo can be caused by problems in the inner ear or central nervous system. The diagnosis of inner ear disorders begins with a targeted physical examination. The initial work-up of hearing loss is made by audiometry, and vertigo by electronystagmography (ENG). Supplemental tests and MRI are obtained when clinically indicated. The clinical pattern and duration of vertigo are the most important clinical features in the diagnosis. Common inner ear causes of vertigo include: vestibular neuritis (sudden, unilateral vestibular loss), Meniere's disease (episodic vertigo), benign paroxysmal positional vertigo (BPPV), and bilateral vestibular loss. Common central nervous system causes of vertigo include: post concussion syndrome, cervical vertigo, vestibular migraine, cerebrovascular disease, and acoustic neuroma. A basic knowledge of vestibular physiology, coupled with a understanding of common vestibular syndromes, will lead to correct diagnosis and treatment in most cases.

  20. Histone deacetylase 1 is required for the development of the zebrafish inner ear

    PubMed Central

    He, Yingzi; Tang, Dongmei; Li, Wenyan; Chai, Renjie; Li, Huawei

    2016-01-01

    Histone deacetylase 1 (HDAC1) has been reported to be important for multiple aspects of normal embryonic development, but little is known about its function in the development of mechanosensory organs. Here, we first confirmed that HDAC1 is expressed in the developing otic vesicles of zebrafish by whole-mount in situ hybridization. Knockdown of HDAC1 using antisense morpholino oligonucleotides in zebrafish embryos induced smaller otic vesicles, abnormal otoliths, malformed or absent semicircular canals, and fewer sensory hair cells. HDAC1 loss of function also caused attenuated expression of a subset of key genes required for otic vesicle formation during development. Morpholino-mediated knockdown of HDAC1 resulted in decreased expression of members of the Fgf family in the otic vesicles, suggesting that HDAC1 is involved in the development of the inner ear through regulation of Fgf signaling pathways. Taken together, our results indicate that HDAC1 plays an important role in otic vesicle formation. PMID:26832938

  1. Exposure to non-ionizing electromagnetic fields emitted from mobile phones induced DNA damage in human ear canal hair follicle cells.

    PubMed

    Akdag, Mehmet; Dasdag, Suleyman; Canturk, Fazile; Akdag, Mehmet Zulkuf

    2018-01-01

    The aim of this study was to investigate effect of radiofrequency radiation (RFR) emitted from mobile phones on DNA damage in follicle cells of hair in the ear canal. The study was carried out on 56 men (age range: 30-60 years old)in four treatment groups with n = 14 in each group. The groups were defined as follows: people who did not use a mobile phone (Control), people use mobile phones for 0-30 min/day (second group), people use mobile phones for 30-60 min/day (third group) and people use mobile phones for more than 60 min/day (fourth group). Ear canal hair follicle cells taken from the subjects were analyzed by the Comet Assay to determine DNA damages. The Comet Assay parameters measured were head length, tail length, comet length, percentage of head DNA, tail DNA percentage, tail moment, and Olive tail moment. Results of the study showed that DNA damage indicators were higher in the RFR exposure groups than in the control subjects. In addition, DNA damage increased with the daily duration of exposure. In conclusion, RFR emitted from mobile phones has a potential to produce DNA damage in follicle cells of hair in the ear canal. Therefore, mobile phone users have to pay more attention when using wireless phones.

  2. A biophysical signature of network affiliation and sensory processing in mitral cells

    PubMed Central

    Angelo, Kamilla; Rancz, Ede A.; Pimentel, Diogo; Hundahl, Christian; Hannibal, Jens; Fleischmann, Alexander; Pichler, Bruno; Margrie, Troy W.

    2012-01-01

    One defining characteristic of the mammalian brain is its neuronal diversity1. For a given region, substructure or layer and even cell type2, variability in neuronal morphology and connectivity2-5 persists. While it is well established that such cellular properties vary considerably according to neuronal type, the significant biophysical diversity of neurons of the same morphological class is typically averaged out and ignored. Here we show that the amplitude of hyperpolarization-evoked membrane potential sag recorded in olfactory bulb mitral cells is an emergent, homotypic property of local networks and sensory information processing. Simultaneous whole-cell recordings from pairs of cells reveal that the amount of hyperpolarization-evoked sag potential and current6 is stereotypic for mitral cells belonging to the same glomerular circuit. This is corroborated by a mosaic, glomerulus-based pattern of expression of the HCN2 subunit of the hyperpolarization-activated current (Ih) channel. Furthermore, inter-glomerular differences in both membrane potential sag and HCN2 protein are diminished when sensory input to glomeruli is genetically and globally altered so only one type of odorant receptor is universally expressed7. We therefore suggest that population diversity in the intrinsic profile of mitral cells reflect functional adaptations of distinct local circuits dedicated to processing subtly different odor-related information. PMID:22820253

  3. Ontogenetic development of the inner ear saccule and utricle in the Lusitanian toadfish: Potential implications for auditory sensitivity.

    PubMed

    Chaves, Patrícia P; Valdoria, Ciara M C; Amorim, M Clara P; Vasconcelos, Raquel O

    2017-09-01

    Studies addressing structure-function relationships of the fish auditory system during development are sparse compared to other taxa. The Batrachoididae has become an important group to investigate mechanisms of auditory plasticity and evolution of auditory-vocal systems. A recent study reported ontogenetic improvements in the inner ear saccule sensitivity of the Lusitanian toadfish, Halobatrachus didactylus, but whether this results from changes in the sensory morphology remains unknown. We investigated how the macula and organization of auditory receptors in the saccule and utricle change during growth in this species. Inner ear sensory epithelia were removed from the end organs of previously PFA-fixed specimens, from non-vocal posthatch fry (<1.4 cm, standard length) to adults (>23 cm). Epithelia were phalloidin-stained and analysed for area, shape, number and orientation patterns of hair cells (HC), and number and size of saccular supporting cells (SC). Saccular macula area expanded 41x in total, and significantly more (relative to body length) among vocal juveniles (2.3-2.9 cm). Saccular HC number increased 25x but HC density decreased, suggesting that HC addition is slower relative to epithelial growth. While SC density decreased, SC apical area increased, contributing to the epithelial expansion. The utricule revealed increased HC density (striolar region) and less epithelial expansion (5x) with growth, contrasting with the saccule that may have a different developmental pattern due to its larger size and main auditory functions. Both macula shape and HC orientation patterns were already established in the posthatch fry and retained throughout growth in both end organs. We suggest that previously reported ontogenetic improvements in saccular sensitivity might be associated with changes in HC number (not density), size and/or molecular mechanisms controlling HC sensitivity. This is one of the first studies investigating the ontogenetic development of the

  4. Ear Tubes

    MedlinePlus

    ... 1/20th of an inch) that could allow water to enter the middle ear, research studies show no benefit in keeping the ears dry and current guidelines do not recommend routine water precautions. Therefore, you do not need to restrict ...

  5. Restrictions in Cell Cycle Progression of Adult Vestibular Supporting Cells in Response to Ectopic Cyclin D1 Expression

    PubMed Central

    Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H.; Pirvola, Ulla

    2011-01-01

    Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27Kip1 and p21Cip1 expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells. PMID:22073316

  6. Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.

    PubMed

    Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H; Pirvola, Ulla

    2011-01-01

    Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27(Kip1) and p21(Cip1) expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells.

  7. Reprogramming of single-cell derived mesenchymal stem cells into hair cell-like cells

    PubMed Central

    Lin, Zhaoyu; Perez, Philip; Sun, Zhenyu; Liu, Jan-Jan; Shin, June Ho; Hyrc, Krzysztof L.; Samways, Damien; Egan, Terry; Holley, Matthew C.; Bao, Jianxin

    2012-01-01

    Hypothesis Adult mesenchymal stem cells (MSCs) can be converted into hair cell-like cells by transdetermination. Background Given the fundamental role sensory hair cells play in sound detection and the irreversibility of their loss in mammals, much research has focused on developing methods to generate new hair cells as a means of treating permanent hearing loss. Although MSCs can differentiate into multiple cell lineages, no efficient means of reprogramming them into sensory hair cells exists. Earlier work has shown that the transcription factor Atoh1 is necessary for early development of hair cells, but it is not clear whether Atoh1 can be used to convert MSCs into hair cells. Methods Clonal MSC cell lines were established and reprogrammed into hair cell-like cells by a combination of protein transfer, adenoviral based gene transfer and co-culture with neurons. During transdetermination, inner ear molecular markers were analyzed by RT-PCR, and cell structures were examined by immunocytochemistry. Results Atoh1 overexpression in MSCs failed to convert MSCs into hair cell-like cells, suggesting that the ability of Atoh1 to induce hair cell differentiation is context dependent. Because Atoh1 overexpression successfully transforms VOT-E36 cells into hair cell-like cells, we modified the cell context of MSCs by performing a total protein transfer from VOT-E36 cells prior to overexpressing Atoh1. The modified MSCs were transformed into hair cell-like cells and attracted contacts from spiral ganglion neurons in a co-culture model. Conclusion We established a new procedure, consisting of VOT-E36 protein transfer, Atoh1 overexpression, and co-culture with spiral ganglion neurons, which can transform MSCs into hair cell-like cells. PMID:23111404

  8. Ear canal dynamic motion as a source of power for in-ear devices

    NASA Astrophysics Data System (ADS)

    Delnavaz, Aidin; Voix, Jérémie

    2013-02-01

    Ear canal deformation caused by temporomandibular joint (jaw joint) activity, also known as "ear canal dynamic motion," is introduced in this paper as a candidate source of power to possibly recharge hearing aid batteries. The geometrical deformation of the ear canal is quantified in 3D by laser scanning of different custom ear moulds. An experimental setup is proposed to measure the amount of power potentially available from this source. The results show that 9 mW of power is available from a 15 mm3 dynamic change in the ear canal volume. Finally, the dynamic motion and power capability of the ear canal are investigated in a group of 12 subjects.

  9. Characterizing Human Stem Cell–derived Sensory Neurons at the Single-cell Level Reveals Their Ion Channel Expression and Utility in Pain Research

    PubMed Central

    Young, Gareth T; Gutteridge, Alex; Fox, Heather DE; Wilbrey, Anna L; Cao, Lishuang; Cho, Lily T; Brown, Adam R; Benn, Caroline L; Kammonen, Laura R; Friedman, Julia H; Bictash, Magda; Whiting, Paul; Bilsland, James G; Stevens, Edward B

    2014-01-01

    The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell–derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders. PMID:24832007

  10. Mate choice in the eye and ear of the beholder? Female multimodal sensory configuration influences her preferences.

    PubMed

    Ronald, Kelly L; Fernández-Juricic, Esteban; Lucas, Jeffrey R

    2018-05-16

    A common assumption in sexual selection studies is that receivers decode signal information similarly. However, receivers may vary in how they rank signallers if signal perception varies with an individual's sensory configuration. Furthermore, receivers may vary in their weighting of different elements of multimodal signals based on their sensory configuration. This could lead to complex levels of selection on signalling traits. We tested whether multimodal sensory configuration could affect preferences for multimodal signals. We used brown-headed cowbird ( Molothrus ater ) females to examine how auditory sensitivity and auditory filters, which influence auditory spectral and temporal resolution, affect song preferences, and how visual spatial resolution and visual temporal resolution, which influence resolution of a moving visual signal, affect visual display preferences. Our results show that multimodal sensory configuration significantly affects preferences for male displays: females with better auditory temporal resolution preferred songs that were shorter, with lower Wiener entropy, and higher frequency; and females with better visual temporal resolution preferred males with less intense visual displays. Our findings provide new insights into mate-choice decisions and receiver signal processing. Furthermore, our results challenge a long-standing assumption in animal communication which can affect how we address honest signalling, assortative mating and sensory drive. © 2018 The Author(s).

  11. External Otitis (Swimmer's Ear)

    MedlinePlus

    ... Debris removal, antibiotic ear drops, keeping water and cotton swabs out of the ear, and pain relievers ... Injuring the ear canal while cleaning it (using cotton swabs) or getting water or irritants, such as ...

  12. Ear Injuries (For Parents)

    MedlinePlus

    ... Inserting something into the ear. Things like a cotton swab, fingernail, or pencil can scratch the ear ... Never stick anything in their ears — not even cotton swabs or their fingers. Regular bathing should be ...

  13. Cytodifferentiation of hair cells during the development of a basal chordate.

    PubMed

    Gasparini, Fabio; Caicci, Federico; Rigon, Francesca; Zaniolo, Giovanna; Burighel, Paolo; Manni, Lucia

    2013-10-01

    Tunicates are unique animals for studying the origin and evolution of vertebrates because they are considered vertebrates' closest living relatives and share the vertebrate body plan and many specific features. Both possess neural placodes, transient thickenings of the cranial ectoderm that give rise to various types of sensory cells, including axonless secondary mechanoreceptors. In vertebrates, these are represented by the hair cells of the inner ear and the lateral line, which have an apical apparatus typically bearing cilia and stereovilli. In tunicates, they are found in the coronal organ, which is a mechanoreceptor located at the base of the oral siphon along the border of the velum and tentacles and is formed of cells bearing a row of cilia and short microvilli. The coronal organ represents the best candidate homolog for the vertebrate lateral line. To further understand the evolution of secondary sensory cells, we analysed the development and cytodifferentiation of coronal cells in the tunicate ascidian Ciona intestinalis for the first time. Here, coronal sensory cells can be identified as early as larval metamorphosis, before tentacles form, as cells with short cilia and microvilli. Sensory cells gradually differentiate, acquiring hair cell features with microvilli containing actin and myosin VIIa; in the meantime, the associated supporting cells develop. The coronal organ grows throughout the animal's lifespan, accompanying the growth of the tentacle crown. Anti-phospho Histone H3 immunostaining indicates that both hair cells and supporting cells can proliferate. This finding contributes to the understanding of the evolution of secondary sensory cells, suggesting that both ancestral cell types were able to proliferate and that this property was progressively restricted to supporting cells in vertebrates and definitively lost in mammals. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Sox10 Expressing Cells in the Lateral Wall of the Aged Mouse and Human Cochlea

    PubMed Central

    Hao, Xinping; Xing, Yazhi; Moore, Michael W.; Zhang, Jianning; Han, Demin; Schulte, Bradley A.; Dubno, Judy R.; Lang, Hainan

    2014-01-01

    Age-related hearing loss (presbycusis) is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1–3 month-old) and aged (2–2.5 year-old) mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10+ cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells) in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10+ marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10+ cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10+ cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10+ cells may also be associated with a decline in the repair capabilities of non-sensory cells in the aged ear. PMID

  15. Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices

    PubMed Central

    Tremblay, Marie-Ève; Zettel, Martha L.; Ison, James R.; Allen, Paul D.; Majewska, Ania K.

    2011-01-01

    Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age-related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age-related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age-related sensory loss. Together, our results suggest that the age-related alteration of glial cells in sensory cortical areas can be accelerated by activity-driven central mechanisms that result from an age-related loss of peripheral sensitivity. In light of our observations, these age-related changes in sensory function should be considered when investigating cellular, cortical and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models. PMID:22223464

  16. L-Amino Acids Elicit Diverse Response Patterns in Taste Sensory Cells: A Role for Multiple Receptors

    PubMed Central

    Pal Choudhuri, Shreoshi; Delay, Rona J.; Delay, Eugene R.

    2015-01-01

    Umami, the fifth basic taste, is elicited by the L-amino acid, glutamate. A unique characteristic of umami taste is the response potentiation by 5’ ribonucleotide monophosphates, which are also capable of eliciting an umami taste. Initial reports using human embryonic kidney (HEK) cells suggested that there is one broadly tuned receptor heterodimer, T1r1+T1r3, which detects L-glutamate and all other L-amino acids. However, there is growing evidence that multiple receptors detect glutamate in the oral cavity. While much is understood about glutamate transduction, the mechanisms for detecting the tastes of other L-amino acids are less well understood. We used calcium imaging of isolated taste sensory cells and taste cell clusters from the circumvallate and foliate papillae of C57BL/6J and T1r3 knockout mice to determine if other receptors might also be involved in detection of L-amino acids. Ratiometric imaging with Fura-2 was used to study calcium responses to monopotassium L-glutamate, L-serine, L-arginine, and L-glutamine, with and without inosine 5’ monophosphate (IMP). The results of these experiments showed that the response patterns elicited by L-amino acids varied significantly across taste sensory cells. L-amino acids other than glutamate also elicited synergistic responses in a subset of taste sensory cells. Along with its role in synergism, IMP alone elicited a response in a large number of taste sensory cells. Our data indicate that synergistic and non-synergistic responses to L-amino acids and IMP are mediated by multiple receptors or possibly a receptor complex. PMID:26110622

  17. Chinchilla middle ear transmission matrix model and middle-ear flexibilitya)

    PubMed Central

    Ravicz, Michael E.; Rosowski, John J.

    2017-01-01

    The function of the middle ear (ME) in transforming ME acoustic inputs and outputs (sound pressures and volume velocities) can be described with an acoustic two-port transmission matrix. This description is independent of the load on the ME (cochlea or ear canal) and holds in either direction: forward (from ear canal to cochlea) or reverse (from cochlea to ear canal). A transmission matrix describing ME function in chinchilla, an animal commonly used in auditory research, is presented, computed from measurements of forward ME function: input admittance YTM, ME pressure gain GMEP, ME velocity transfer function HV, and cochlear input admittance YC, in the same set of ears [Ravicz and Rosowski (2012b). J. Acoust. Soc. Am. 132, 2437–2454; (2013a). J. Acoust. Soc. Am. 133, 2208–2223; (2013b). J. Acoust. Soc. Am. 134, 2852–2865]. Unlike previous estimates, these computations require no assumptions about the state of the inner ear, effectiveness of ME manipulations, or measurements of sound transmission in the reverse direction. These element values are generally consistent with physical constraints and the anatomical ME “transformer ratio.” Differences from a previous estimate in chinchilla [Songer and Rosowski (2007). J. Acoust. Soc. Am. 122, 932–942] may be due to a difference in ME flexibility between the two subject groups. PMID:28599566

  18. Chinchilla middle ear transmission matrix model and middle-ear flexibility.

    PubMed

    Ravicz, Michael E; Rosowski, John J

    2017-05-01

    The function of the middle ear (ME) in transforming ME acoustic inputs and outputs (sound pressures and volume velocities) can be described with an acoustic two-port transmission matrix. This description is independent of the load on the ME (cochlea or ear canal) and holds in either direction: forward (from ear canal to cochlea) or reverse (from cochlea to ear canal). A transmission matrix describing ME function in chinchilla, an animal commonly used in auditory research, is presented, computed from measurements of forward ME function: input admittance Y TM , ME pressure gain G MEP , ME velocity transfer function H V , and cochlear input admittance Y C , in the same set of ears [Ravicz and Rosowski (2012b). J. Acoust. Soc. Am. 132, 2437-2454; (2013a). J. Acoust. Soc. Am. 133, 2208-2223; (2013b). J. Acoust. Soc. Am. 134, 2852-2865]. Unlike previous estimates, these computations require no assumptions about the state of the inner ear, effectiveness of ME manipulations, or measurements of sound transmission in the reverse direction. These element values are generally consistent with physical constraints and the anatomical ME "transformer ratio." Differences from a previous estimate in chinchilla [Songer and Rosowski (2007). J. Acoust. Soc. Am. 122, 932-942] may be due to a difference in ME flexibility between the two subject groups.

  19. Conversion of neurons and glia to external-cell fates in the external sensory organs of Drosophila hamlet mutants by a cousin-cousin cell-type respecification.

    PubMed

    Moore, Adrian W; Roegiers, Fabrice; Jan, Lily Y; Jan, Yuh-Nung

    2004-03-15

    The Drosophila external sensory organ forms in a lineage elaborating from a single precursor cell via a stereotypical series of asymmetric divisions. HAMLET transcription factor expression demarcates the lineage branch that generates two internal cell types, the external sensory neuron and thecogen. In HAMLET mutant organs, these internal cells are converted to external cells via an unprecedented cousin-cousin cell-fate respecification event. Conversely, ectopic HAMLET expression in the external cell branch leads to internal cell production. The fate-determining signals NOTCH and PAX2 act at multiple stages of lineage elaboration and HAMLET acts to modulate their activity in a branch-specific manner.

  20. Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing

    PubMed Central

    Liu, Hongzhuo; Feng, Liang; Tolia, Gaurav; Liddell, Mark R.; Hao, Jinsong; Li, S. Kevin

    2013-01-01

    A convenient and efficient in vitro diffusion cell method to evaluate formulations for inner ear delivery via the intratympanic route is currently not available. The existing in vitro diffusion cell systems commonly used to evaluate drug formulations do not resemble the physical dimensions of the middle ear and round window membrane. The objectives of this study were to examine a modified in vitro diffusion cell system of a small diffusion area for studying sustained release formulations in inner ear drug delivery and to identify a formulation for sustained drug delivery to the inner ear. Four formulations and a control were examined in this study using cidofovir as the model drug. Drug release from the formulations in the modified diffusion cell system was slower than that in the conventional diffusion cell system due to the decrease in the diffusion surface area of the modified diffusion cell system. The modified diffusion cell system was able to show different drug release behaviors among the formulations and allowed formulation evaluation better than the conventional diffusion cell system. Among the formulations investigated, poly(lactic-co-glycolic acid)–poly(ethylene glycol)–poly(lactic-co-glycolic acid) triblock copolymer systems provided the longest sustained drug delivery, probably due to their rigid gel structures and/or polymer-to-cidofovir interactions. PMID:23631539

  1. In vivo and in vitro biophysical properties of hair cells from the lateral line and inner ear of developing and adult zebrafish.

    PubMed

    Olt, Jennifer; Johnson, Stuart L; Marcotti, Walter

    2014-05-15

    Hair cells detect and process sound and movement information, and transmit this with remarkable precision and efficiency to afferent neurons via specialized ribbon synapses. The zebrafish is emerging as a powerful model for genetic analysis of hair cell development and function both in vitro and in vivo. However, the full exploitation of the zebrafish is currently limited by the difficulty in obtaining systematic electrophysiological recordings from hair cells under physiological recording conditions. Thus, the biophysical properties of developing and adult zebrafish hair cells are largely unknown. We investigated potassium and calcium currents, voltage responses and synaptic activity in hair cells from the lateral line and inner ear in vivo and using near-physiological in vitro recordings. We found that the basolateral current profile of hair cells from the lateral line becomes more segregated with age, and that cells positioned in the centre of the neuromast show more mature characteristics and those towards the edge retain a more immature phenotype. The proportion of mature-like hair cells within a given neuromast increased with zebrafish development. Hair cells from the inner ear showed a developmental change in current profile between the juvenile and adult stages. In lateral line hair cells from juvenile zebrafish, exocytosis also became more efficient and required less calcium for vesicle fusion. In hair cells from mature zebrafish, the biophysical characteristics of ion channels and exocytosis resembled those of hair cells from other lower vertebrates and, to some extent, those in the immature mammalian vestibular and auditory systems. We show that although the zebrafish provides a suitable animal model for studies on hair cell physiology, it is advisable to consider that the age at which the majority of hair cells acquire a mature-type configuration is reached only in the juvenile lateral line and in the inner ear from >2 months after hatching. © 2014 The

  2. Taking Care of Your Ears

    MedlinePlus

    ... Audiologist Perforated Eardrum What's Hearing Loss? Can Loud Music Hurt My Ears? What Is an Ear Infection? Swimmer's Ear Your Ears What's Earwax? View more About Us Contact Us Partners Editorial Policy Permissions Guidelines Privacy Policy & Terms of Use Notice ...

  3. KGFR as a possible therapeutic target in middle ear cholesteatoma.

    PubMed

    Yamamoto-Fukuda, Tomomi; Akiyama, Naotaro; Shibata, Yasuaki; Takahashi, Haruo; Ikeda, Tohru; Kohno, Michiaki; Koji, Takehiko

    2014-11-01

    We demonstrated that repression of keratinocyte growth factor (KGF) receptor (KGFR) could be a potentially useful strategy in the conservative treatment of middle ear cholesteatoma. Recently, the use of a selective inhibitor of the KGFR, SU5402, in an in vitro experiment resulted in the inhibition of the differentiation and proliferation of epithelial cells through KGF secretion by fibroblasts isolated from the cholesteatoma. In this study, we investigated the effects of the KGFR inhibitor during middle ear cholesteatoma formation in vivo. Based on the role of KGF in the development of cholesteatoma, Flag-hKGF cDNA driven by CMV14 promoter was transfected through electroporation into the external auditory canal of rats five times on every fourth day. Ears transfected with empty vector were used as controls. KGFR selective inhibitor (SU5402) or MEK inhibitor (PD0325901) was administered in the right ear of five rats after vector transfection. In the control, 2% DMSO in PBS was administered in the other ears after vector transfection. The use of a selective KGFR inhibitor, SU5402, completely prevented middle ear cholesteatoma formation in the rats.

  4. Middle Ear Infections (For Parents)

    MedlinePlus

    ... Staying Safe Videos for Educators Search English Español Middle Ear Infections KidsHealth / For Parents / Middle Ear Infections What's ... en español Infecciones del oído medio What Are Middle Ear Infections? Ear infections happen when viruses or bacteria ...

  5. Transcriptomic insights into citrus segment membrane's cell wall components relating to fruit sensory texture.

    PubMed

    Wang, Xun; Lin, Lijin; Tang, Yi; Xia, Hui; Zhang, Xiancong; Yue, Maolan; Qiu, Xia; Xu, Ke; Wang, Zhihui

    2018-04-23

    During fresh fruit consumption, sensory texture is one factor that affects the organoleptic qualities. Chemical components of plant cell walls, including pectin, cellulose, hemicellulose and lignin, play central roles in determining the textural qualities. To explore the genes and regulatory pathways involved in fresh citrus' perceived sensory texture, we performed mRNA-seq analyses of the segment membranes of two citrus cultivars, Shiranui and Kiyomi, with different organoleptic textures. Segment membranes were sampled at two developmental stages of citrus fruit, the beginning and end of the expansion period. More than 3000 differentially expressed genes were identified. The gene ontology analysis revealed that more categories were significantly enriched in 'Shiranui' than in 'Kiyomi' at both developmental stages. In total, 108 significantly enriched pathways were obtained, with most belonging to metabolism. A detailed transcriptomic analysis revealed potential critical genes involved in the metabolism of cell wall structures, for example, GAUT4 in pectin synthesis, CESA1, 3 and 6, and SUS4 in cellulose synthesis, CSLC5, XXT1 and XXT2 in hemicellulose synthesis, and CSE in lignin synthesis. Low levels, or no expression, of genes involved in cellulose and hemicellulose, such as CESA4, CESA7, CESA8, IRX9 and IRX14, confirmed that secondary cell walls were negligible or absent in citrus segment membranes. A chemical component analysis of the segment membranes from mature fruit revealed that the pectin, cellulose and lignin contents, and the segment membrane's weight (% of segment) were greater in 'Kiyomi'. Organoleptic quality of citrus is easily overlooked. It is mainly determined by sensory texture perceived in citrus segment membrane properties. We performed mRNA-seq analyses of citrus segment membranes to explore the genes and regulatory pathways involved in fresh citrus' perceived sensory texture. Transcriptomic data showed high repeatability between two

  6. Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction.

    PubMed

    Sotomayor, Marcos; Weihofen, Wilhelm A; Gaudet, Rachelle; Corey, David P

    2012-12-06

    Hearing and balance use hair cells in the inner ear to transform mechanical stimuli into electrical signals. Mechanical force from sound waves or head movements is conveyed to hair-cell transduction channels by tip links, fine filaments formed by two atypical cadherins known as protocadherin 15 and cadherin 23 (refs 4, 5). These two proteins are involved in inherited deafness and feature long extracellular domains that interact tip-to-tip in a Ca(2+)-dependent manner. However, the molecular architecture of this complex is unknown. Here we combine crystallography, molecular dynamics simulations and binding experiments to characterize the protocadherin 15-cadherin 23 bond. We find a unique cadherin interaction mechanism, in which the two most amino-terminal cadherin repeats (extracellular cadherin repeats 1 and 2) of each protein interact to form an overlapped, antiparallel heterodimer. Simulations predict that this tip-link bond is mechanically strong enough to resist forces in hair cells. In addition, the complex is shown to become unstable in response to Ca(2+) removal owing to increased flexure of Ca(2+)-free cadherin repeats. Finally, we use structures and biochemical measurements to study the molecular mechanisms by which deafness mutations disrupt tip-link function. Overall, our results shed light on the molecular mechanics of hair-cell sensory transduction and on new interaction mechanisms for cadherins, a large protein family implicated in tissue and organ morphogenesis, neural connectivity and cancer.

  7. Temporal and spatial expression patterns of Hedgehog receptors in the developing inner and middle ear.

    PubMed

    Shin, Jeong-Oh; Ankamreddy, Harinarayana; Jakka, Naga Mahesh; Lee, Seokwon; Kim, Un-Kyung; Bok, Jinwoong

    2017-01-01

    The mammalian inner ear is a complex organ responsible for balance and hearing. Sonic hedgehog (Shh), a member of the Hedgehog (Hh) family of secreted proteins, has been shown to play important roles in several aspects of inner ear development, including dorsoventral axial specification, cochlear elongation, tonotopic patterning, and hair cell differentiation. Hh proteins initiate a downstream signaling cascade by binding to the Patched 1 (Ptch1) receptor. Recent studies have revealed that other types of co-receptors can also mediate Hh signaling, including growth arrest-specific 1 (Gas1), cell-adhesion molecules-related/down-regulated by oncogenes (Cdon), and biregional Cdon binding protein (Boc). However, little is known about the role of these Hh co-receptors in inner ear development. In this study, we examined the expression patterns of Gas1, Cdon, and Boc, as well as that of Ptch1, in the developing mouse inner ear from otocyst (embryonic day (E) 9.5) until birth and in the developing middle ear at E15.5. Ptch1, a readout of Hh signaling, was expressed in a graded pattern in response to Shh signaling throughout development. Expression patterns of Gas1, Cdon, and Boc differed from that of Ptch1, and each Hh co-receptor was expressed in specific cells and domains in the developing inner and middle ear. These unique and differential expression patterns of Hh co-receptors suggest their roles in mediating various time- and space-specific functions of Shh during ear development.

  8. Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices.

    PubMed

    Tremblay, Marie-Ève; Zettel, Martha L; Ison, James R; Allen, Paul D; Majewska, Ania K

    2012-04-01

    Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age-related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age-related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age-related sensory loss. Together, our results suggest that the age-related alteration of glial cells in sensory cortical areas can be accelerated by activity-driven central mechanisms that result from an age-related loss of peripheral sensitivity. In light of our observations, these age-related changes in sensory function should be considered when investigating cellular, cortical, and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models. Copyright © 2012 Wiley Periodicals, Inc.

  9. The stat3/socs3a pathway is a key regulator of hair cell regeneration in zebrafish. [corrected].

    PubMed

    Liang, Jin; Wang, Dongmei; Renaud, Gabriel; Wolfsberg, Tyra G; Wilson, Alexander F; Burgess, Shawn M

    2012-08-01

    All nonmammalian vertebrates studied can regenerate inner ear mechanosensory receptors (i.e., hair cells) (Corwin and Cotanche, 1988; Lombarte et al., 1993; Baird et al., 1996), but mammals possess only a very limited capacity for regeneration after birth (Roberson and Rubel, 1994). As a result, mammals experience permanent deficiencies in hearing and balance once their inner ear hair cells are lost. The mechanisms of hair cell regeneration are poorly understood. Because the inner ear sensory epithelium is highly conserved in all vertebrates (Fritzsch et al., 2007), we chose to study hair cell regeneration mechanism in adult zebrafish, hoping the results would be transferrable to inducing hair cell regeneration in mammals. We defined the comprehensive network of genes involved in hair cell regeneration in the inner ear of adult zebrafish with the powerful transcriptional profiling technique digital gene expression, which leverages the power of next-generation sequencing ('t Hoen et al., 2008). We also identified a key pathway, stat3/socs3, and demonstrated its role in promoting hair cell regeneration through stem cell activation, cell division, and differentiation. In addition, transient pharmacological inhibition of stat3 signaling accelerated hair cell regeneration without overproducing cells. Taking other published datasets into account (Sano et al., 1999; Schebesta et al., 2006; Dierssen et al., 2008; Riehle et al., 2008; Zhu et al., 2008; Qin et al., 2009), we propose that the stat3/socs3 pathway is a key response in all tissue regeneration and thus an important therapeutic target for a broad application in tissue repair and injury healing.

  10. Cauliflower ear dissection.

    PubMed

    Fujiwara, Masao; Suzuki, Ayano; Nagata, Takeshi; Fukamizu, Hidekazu

    2011-11-01

    Cauliflower ear (CE) is caused by repeated direct trauma to the external ear. Surgical correction of an established CE is one of the most challenging problems in ear reconstruction. However, no reports have clarified the dissection of an established CE in detail. In this report, the dissection of a CE is described based on macroscopic, microscopic and imaging features. Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  11. Body-conscious Shakespeare: sensory disturbances in troubled characters.

    PubMed

    Heaton, Kenneth W

    2011-12-01

    It is widely accepted that Shakespeare was unique in the range of his insights into the human mind, but the way his characters reveal their mental states through bodily sensations has not been systematically explored. The author has searched for these phenomena in the 42 major works of Shakespeare and in 46 genre-matched works by his contemporaries, and in this paper the author focuses on sensory changes other than those involving vision, taste, the heart and the alimentary tract (all considered in other papers). Vertigo is experienced by five distressed Shakespearean characters, all men, but not at all by the other writers' characters. Breathlessness, probably representing hyperventilation, occurs eleven times in Shakespeare's works but only twice in the other writers' works. Fatigue, expressing grief, is articulated by several Shakespearean characters including Hamlet. It features less often in the others' works. Deafness at a time of high emotion is mentioned by Shakespeare several times but usually by a character 'turning a deaf ear', consciously or unconsciously. To the other writers, ears show emotion only by burning or itching. Blunting of touch and pain and their opposites of hypersensitivity to touch and pain are all to be found in Shakespeare's works when a character is distressed or excited, but not so with his contemporaries' works. Faint feelings and cold feelings are also more common in the works of Shakespeare. Overall, therefore, Shakespeare was exceptional in his use of sensory disturbances to express emotional upset. This may be a conscious literary device or a sign of exceptional awareness of bodily sensations.

  12. Estimation of outer-middle ear transmission using DPOAEs and fractional-order modeling of human middle ear

    NASA Astrophysics Data System (ADS)

    Naghibolhosseini, Maryam

    Our ability to hear depends primarily on sound waves traveling through the outer and middle ear toward the inner ear. Hence, the characteristics of the outer and middle ear affect sound transmission to/from the inner ear. The role of the middle and outer ear in sound transmission is particularly important for otoacoustic emissions (OAEs), which are sound signals generated in a healthy cochlea, and recorded by a sensitive microphone placed in the ear canal. OAEs are used to evaluate the health and function of the cochlea; however, they are also affected by outer and middle ear characteristics. To better assess cochlear health using OAEs, it is critical to quantify the impact of the outer and middle ear on sound transmission. The reported research introduces a noninvasive approach to estimate outer-middle ear transmission using distortion product otoacoustic emissions (DPOAEs). In addition, the role of the outer and middle ear on sound transmission was investigated by developing a physical/mathematical model, which employed fractional-order lumped elements to include the viscoelastic characteristics of biological tissues. Impedance estimations from wideband refectance measurements were used for parameter fitting of the model. The model was validated comparing its estimates of the outer-middle ear sound transmission with those given by DPOAEs. The outer-middle ear transmission by the model was defined as the sum of forward and reverse outer-middle ear transmissions. To estimate the reverse transmission by the model, the probe-microphone impedance was calculated through estimating the Thevenin-equivalent circuit of the probe-microphone. The Thevenin-equivalent circuit was calculated using measurements in a number of test cavities. Such modeling enhances our understanding of the roles of different parts of the outer and middle ear and how they work together to determine their function. In addition, the model would be potentially helpful in diagnosing pathologies of

  13. Prenatal evaluation of the middle ear and diagnosis of middle ear hypoplasia using MRI.

    PubMed

    Katorza, Eldad; Nahama-Allouche, Catherine; Castaigne, Vanina; Gonzales, Marie; Galliani, Eva; Marlin, Sandrine; Jouannic, Jean-Marie; Rosenblatt, Jonathan; le Pointe, Hubert Ducou; Garel, Catherine

    2011-05-01

    Analysis of the middle ear with fetal MRI has not been previously reported. To show the contribution of fetal MRI to middle ear imaging. The tympanic cavity was evaluated in 108 fetal cerebral MRI examinations (facial and/or cerebral malformation excluded) and in two cases, one of Treacher Collins syndrome (case 1) and the other of oculo-auriculo-vertebral (OUV) spectrum (case 2) with middle ear hypoplasia identified by MRI at 27 and 36 weeks' gestation, respectively. In all 108 fetuses (mean gestational age 32.5 weeks), the tympanic cavity and T2 hypointensity related to the ossicles were well visualised on both sides. Case 1 had micro/retrognathia and bilateral external ear deformity and case 2 had retrognathism with a left low-set and deformed ear. MRI made it possible to recognize the marked hypoplasia of the tympanic cavity, which was bilateral in case 1 and unilateral in case 2. Both syndromes are characterized by craniofacial abnormalities including middle ear hypoplasia, which cannot be diagnosed with US. The middle ear cavity can be visualized with fetal MRI. We emphasize the use of this imaging modality in the diagnosis of middle ear hypoplasia.

  14. An experimental study of inner ear injury in an animal model of eosinophilic otitis media.

    PubMed

    Matsubara, Atsushi; Nishizawa, Hisanori; Kurose, Akira; Nakagawa, Takashi; Takahata, Junko; Sasaki, Akira

    2014-03-01

    As the periods of intratympanic injection of ovalbumin (OVA) to the middle ear became longer, marked eosinophil infiltration in the perilymphatic space was observed. Moreover severe morphological damage of the organ of Corti was observed in the 28-day antigen-stimulation side. These results indicate that eosinophilic inflammation occurred in the inner ear and caused profound hearing loss. The purpose of the present study was to elucidate the inner ear damage in a new animal model of eosinophilic otitis media (EOM) which we recently constructed. We constructed the animal model of EOM by intraperitoneal and intratympanic injection of OVA. Infiltrating cells and the inner ear damage were examined by histological study. In the inner ear, a few eosinophils were seen in the scala tympani of the organ of Corti and the dilation of capillaries of the stria vascularis was observed in the 7-day stimulation side. In the 14-day antigen stimulation side, some eosinophils and macrophages were seen in not only the scala tympani but also the scala vestibule. In the 28-day antigen-stimulation side, severe morphological damage of the organ of Corti and many eosinophils, red blood cells, and plasma cells infiltrating the perilymph were observed.

  15. Sensorial pedagogies, hungry fat cells and the limits of nutritional health education

    PubMed Central

    Sanabria, Emilia

    2015-01-01

    This article examines the way the category of ‘the sensorial' is mobilised across obesity research and care practices for overweight persons in France. The ‘natural' body is understood to have developed mechanisms that motivate eaters to seek out energy-dense foods, a hardwiring that is maladaptive in today's plethoric food environment. The article analyses the feedback models mobilised in scientific literature on the neuroendocrine processes regulating appetite. The analysis of how ‘the sensorial' is studied and used to treat patients provides a vantage point onto the ways foods and bodies transform each other. Recent findings show that fat cells influence metabolism by secreting hormones, revealing that eaters are affected by the materiality of the foods they ingest. ‘The sensorial' functions as a regulator in the feedback mechanisms where social norms regulating foodscapes become enfolded in the molecular processes that control appetite regulation. The article traces the work that the category of ‘the sensorial' does as it flows through the loops and feedbacks between scientific evidence, policy and care. It examines the way pleasure and the sensations of eaters are increasingly foregrounded in French nutritional health promotion strategies in a context where informing eaters is increasingly deemed ineffective. PMID:26157470

  16. The constricted ear.

    PubMed

    Paredes, Alfredo A; Williams, J Kerwin; Elsahy, Nabil I

    2002-04-01

    The constricted ear may be described best as a pursestring closure of the ear. The deformity may include lidding of the upper pole with downward folding, protrusion of the concha, decreased vertical height, and low ear position relative to the face. The goals of surgical correction should include obtaining symmetry and correcting the intra-auricular anatomy. The degree of intervention is based on the severity of the deformity and may range from simple repositioning, soft tissue rearrangement, or manipulation of the cartilage. Multiple surgical techniques are described.

  17. Exploring the mammalian sensory space: co-operations and trade-offs among senses.

    PubMed

    Nummela, Sirpa; Pihlström, Henry; Puolamäki, Kai; Fortelius, Mikael; Hemilä, Simo; Reuter, Tom

    2013-12-01

    The evolution of a particular sensory organ is often discussed with no consideration of the roles played by other senses. Here, we treat mammalian vision, olfaction and hearing as an interconnected whole, a three-dimensional sensory space, evolving in response to ecological challenges. Until now, there has been no quantitative method for estimating how much a particular animal invests in its different senses. We propose an anatomical measure based on sensory organ sizes. Dimensions of functional importance are defined and measured, and normalized in relation to animal mass. For 119 taxonomically and ecologically diverse species, we can define the position of the species in a three-dimensional sensory space. Thus, we can ask questions related to possible trade-off vs. co-operation among senses. More generally, our method allows morphologists to identify sensory organ combinations that are characteristic of particular ecological niches. After normalization for animal size, we note that arboreal mammals tend to have larger eyes and smaller noses than terrestrial mammals. On the other hand, we observe a strong correlation between eyes and ears, indicating that co-operation between vision and hearing is a general mammalian feature. For some groups of mammals we note a correlation, and possible co-operation between olfaction and whiskers.

  18. Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media.

    PubMed

    Samuels, Tina L; Yan, Justin; Khampang, Pawjai; MacKinnon, Alexander; Hong, Wenzhou; Johnston, Nikki; Kerschner, Joseph E

    2016-09-01

    Toll-like receptor signaling activated by bacterial otitis media pathogens in the middle ear has been shown to play a key role in OM susceptibility, pathogenesis and recovery. Recent studies implicate microRNA 146 (miR-146) in regulation of inflammation via negative feedback of toll-like receptor signaling (TLR) in a wide variety of tissues, however its involvement in otitis media is unknown. Human middle ear epithelial cells were stimulated with proinflammatory cytokines, interleukin 1 beta or tumor necrosis factor alpha, for two to twenty-four hours. Middle ear biopsies were collected from children with otitis media with effusion (n = 20), recurrent otitis media (n = 9), and control subjects undergoing cochlear implantation (n = 10). miR-146a, miR-146b expression was assayed by quantitative PCR (qPCR). Expression of miR-146 targets involved in TLR signaling, IRAK1 and TRAF6, was assayed by qPCR in middle ear biopsies. Middle ear biopsies were cryosectioned and epithelial thickness measured by a certified pathologist. Proinflammatory cytokines induced expression of miR-146 in middle ear epithelial cells in vitro. Middle ear miR-146a and miR-146b expression was elevated in otitis media patients relative to control subjects and correlated with middle ear epithelial thickness. A trend towards inverse correlation was observed between miR-146 and TRAF6 expression in the clinical population. This report is the first to assess miRNA expression in a clinical population with OM. Findings herein suggest miR-146 may play a role in OM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Gustatory otalgia and wet ear syndrome: a possible cross-innervation after ear surgery.

    PubMed

    Saito, H

    1999-04-01

    The chorda tympani and Arnold's nerves have close approximation to each other and their cross-innervation is possible after ear surgery. A retrospective study was performed with a temporal bone pathology case and two clinical cases as representatives of such a possibility. Patients had severe otalgia and wet ear during gustatory stimulation. A temporal bone pathology case was studied under a light microscope. Earache and/or wet ear were provoked during gustatory stimulation. Wet ear was tested with iodine-starch reaction after the subject tasted lemon juice. The temporal bone specimen has clusters of regenerated fibers in the tympanic cavity in the area of the chorda tympani and Arnold's nerves, suggesting a possibility of mixing. There are regenerated fibers in the iter chordae anterius, showing successful bridging of the chorda tympani nerves across a long gap. Detachment of the skin over the operated mastoid bowl obscured signs in one clinical case. Another clinical case of gustatory wet ear showed objective evidence of cross-innervation with iodine-starch reaction. The detachment procedure and iodine-starch reaction were the proofs that the signs were related to regenerated fibers. This is the first report of gustatory otalgia and wet ear after ear surgery.

  20. Responses to Cell Loss Become Restricted as the Supporting Cells in Mammalian Vestibular Organs Grow Thick Junctional Actin Bands That Develop High Stability

    PubMed Central

    Burns, Joseph C.

    2014-01-01

    Sensory hair cell (HC) loss is a major cause of permanent hearing and balance impairments for humans and other mammals. Yet, fish, amphibians, reptiles, and birds readily replace HCs and recover from such sensory deficits. It is unknown what prevents replacement in mammals, but cell replacement capacity declines contemporaneously with massive postnatal thickening of F-actin bands at the junctions between vestibular supporting cells (SCs). In non-mammals, SCs can give rise to regenerated HCs, and the bands remain thin even in adults. Here we investigated the stability of the F-actin bands between SCs in ears from chickens and mice and Madin-Darby canine kidney cells. Pharmacological experiments and fluorescence recovery after photobleaching (FRAP) of SC junctions in utricles from mice that express a γ-actin–GFP fusion protein showed that the thickening F-actin bands develop increased resistance to depolymerization and exceptional stability that parallels a sharp decline in the cell replacement capacity of the maturing mammalian ear. The FRAP recovery rate and the mobile fraction of γ-actin–GFP both decreased as the bands thickened with age and became highly stabilized. In utricles from neonatal mice, time-lapse recordings in the vicinity of dying HCs showed that numerous SCs change shape and organize multicellular actin purse strings that reseal the epithelium. In contrast, adult SCs appeared resistant to deformation, with resealing responses limited to just a few neighboring SCs that did not form purse strings. The exceptional stability of the uniquely thick F-actin bands at the junctions of mature SCs may play an important role in restricting dynamic repair responses in mammalian vestibular epithelia. PMID:24478379

  1. Responses to cell loss become restricted as the supporting cells in mammalian vestibular organs grow thick junctional actin bands that develop high stability.

    PubMed

    Burns, Joseph C; Corwin, Jeffrey T

    2014-01-29

    Sensory hair cell (HC) loss is a major cause of permanent hearing and balance impairments for humans and other mammals. Yet, fish, amphibians, reptiles, and birds readily replace HCs and recover from such sensory deficits. It is unknown what prevents replacement in mammals, but cell replacement capacity declines contemporaneously with massive postnatal thickening of F-actin bands at the junctions between vestibular supporting cells (SCs). In non-mammals, SCs can give rise to regenerated HCs, and the bands remain thin even in adults. Here we investigated the stability of the F-actin bands between SCs in ears from chickens and mice and Madin-Darby canine kidney cells. Pharmacological experiments and fluorescence recovery after photobleaching (FRAP) of SC junctions in utricles from mice that express a γ-actin-GFP fusion protein showed that the thickening F-actin bands develop increased resistance to depolymerization and exceptional stability that parallels a sharp decline in the cell replacement capacity of the maturing mammalian ear. The FRAP recovery rate and the mobile fraction of γ-actin-GFP both decreased as the bands thickened with age and became highly stabilized. In utricles from neonatal mice, time-lapse recordings in the vicinity of dying HCs showed that numerous SCs change shape and organize multicellular actin purse strings that reseal the epithelium. In contrast, adult SCs appeared resistant to deformation, with resealing responses limited to just a few neighboring SCs that did not form purse strings. The exceptional stability of the uniquely thick F-actin bands at the junctions of mature SCs may play an important role in restricting dynamic repair responses in mammalian vestibular epithelia.

  2. Being a Parent's Eyes and Ears: Emotional Literacy and Empathy of Children Whose Parents Have a Sensory Disability

    ERIC Educational Resources Information Center

    Eden, Sigal; Romi, Shlomo; Braun Aviyashar, Einat

    2017-01-01

    Children of parents with sensory disability may feel that their experience helped nurture their sense of empathy. The study was designed to examine the connection between parents' sensory disability (visual disability to blindness and hearing disability to deafness) and the empathy and emotional literacy of their non-sensory-disabled children.…

  3. Ear drainage culture

    MedlinePlus

    ... needed. Your health care provider will use a cotton swab to collect the sample from inside the ... Using a cotton swab to take a sample of drainage from the outer ear is not painful. However, ear pain may ...

  4. Hair cell regeneration: Look to the future

    NASA Astrophysics Data System (ADS)

    Rubel, Edwin W.

    2005-04-01

    Less than 2 decades ago it was discovered that birds can regenerate hair cells in the auditory and vestibular parts of the inner ear after the native hair cells are destroyed by exposure to excessive noise or by mechanical trauma of aminoglycoside antibiotics. This discovery issued in a new era of hearing research-it suggested that some day it may be possible to actually restore hearing in people with congenital or acquired hearing loss due to the degeneration of sensory cells or supporting cells in the inner ear. Fifteen years is a very short time in the history of science. Consider the fact that we have actively sought chemical treatments to prevent or cure cancers for well over a half century and the ``war on Cancer,'' resulted in enormous public and private support. Progress has been great, and some forms of cancer can be treated with great success, but the overall 5-year survival rates have only risen from about 50% to 63%. Progress will continue and many more forms of cancer will be cured and prevented during the next half century. Similarly, during the first 15 years of hair cell regeneration research enormous progress has been made, and we now know that postnatal mammalian ears have the capacity to produce new hair cells. We are indeed a long way from restoring hearing through hair cell regeneration, but the future is pretty clear. I will review the progress of this field with an eye toward the future and what it means for treatments of today. In particular, I will address the potential cost versus benefits of bilateral implantation when applied to babies and young children.

  5. Interrelated striated elements in vestibular hair cells of the rat

    NASA Technical Reports Server (NTRS)

    Ross, M. D.; Bourne, C.

    1983-01-01

    A series of interrelated striated organelles in types I and II vestibular hair cells of the rat which appear to be less developed in cochlear hair cells have been revealed by unusual fixation procedures, suggesting that contractile elements may play a role in sensory transduction in the inner ear, especially in the vestibular system. Included in the series of interrelated striated elements are the cuticular plate and its basal attachments to the hair cell margins, the connections of the strut array of the kinociliary basal body to the cuticular plate, and striated organelles associated with the plasma membrane and extending below the apical junctional complexes.

  6. Ear infection - chronic

    MedlinePlus

    Middle ear infection - chronic; Otitis media - chronic; Chronic otitis media; Chronic ear infection ... Chole RA. Chronic otitis media, mastoiditis, and petrositis. In: Flint PW, Haughey BH, Lund V, et al, eds. Cummings Otolaryngology: Head & Neck Surgery . 6th ed. ...

  7. Caffeic acid phenethyl ester inhibits diesel exhaust particle-induced inflammation of human middle ear epithelial cells via NOX4 inhibition.

    PubMed

    Jo, Sun-Young; Lee, Naree; Hong, Sung-Moon; Jung, Hak Hyun; Chae, Sung-Won

    2013-09-01

    Otitis media is one of the most common diseases in pediatric populations. Recent research on its pathogenesis has focused on air pollution. Chronic exposure to particulate air pollution is associated with the impairment of middle ear function. However, the mechanisms and the underlying inhibitory pathways, especially in the human middle ear, remain unknown. Caffeic acid phenethyl ester (CAPE) is a biologically active ingredient of propolis, a product of honeybee hives, which has anti-oxidative and anti-inflammatory activities. The aim of this study was to evaluate the inhibitory effect of CAPE on diesel exhaust particle (DEP)-induced inflammation of human middle ear epithelial cells and to determine the underlying pathway of the action of CAPE. The inflammatory damage caused by DEPs and the anti-inflammatory effects of CAPE were determined by measuring the levels of tumor necrosis factor alpha and nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4 with real-time reverse transcription polymerase chain reaction and Western blot analysis. The oxidative stress induced by DEPs and the anti-oxidative effects of CAPE were directly evaluated by measuring reactive oxygen species production by use of flow cytometric analysis of 2',7'-dichlorofluorescein diacetate. The effects of CAPE were compared with those of N-acetyl-L-cysteine, which has anti-oxidative and anti-inflammatory effects. Use of CAPE significantly inhibited DEP-induced up-regulation of tumor necrosis factor alpha and NOX4 expression in a dose- and time-dependent manner. The accumulation of reactive oxygen species induced by DEPs was decreased by pretreatment with CAPE. The anti-inflammatory and anti-oxidative effects of CAPE were similar to those of N-acetyl-L-cysteine. The inflammation induced by DEP is reduced by CAPE via the inhibition of NOX4 expression. These findings suggest that CAPE might be used as a therapeutic agent against DEP-induced inflammation of human middle ear epithelial cells.

  8. Oxidative metabolic products released from polymorphonuclear leukocytes in middle ear fluid during experimental pneumococcal otitis media.

    PubMed Central

    Kawana, M; Kawana, C; Yokoo, T; Quie, P G; Giebink, G S

    1991-01-01

    To determine whether oxidative metabolic products of phagocytic cells are present in the middle ear during experimental pneumococcal otitis media, we measured the concentration of myeloperoxidase (MPO) in middle ear fluid (MEF) and the capacity of neutrophils isolated from MEF and peripheral blood to produce MPO and superoxide anion (O2-) after in vitro stimulation. Free MPO in MEF was significantly increased 24 and 48 h after either viable or nonviable pneumococci were inoculated into the middle ear. In vitro-stimulated production of MPO and O2- from middle ear neutrophils was significantly less than that from peripheral blood neutrophils 24 h after nonviable pneumococci were inoculated but similar to it after 48 h. Twenty-four hours after viable pneumococci were inoculated, middle ear neutrophils stimulated in vitro produced less MPO but the same amount of O2- as did blood neutrophils. Oxidative metabolic products, therefore, are released from phagocytic cells into the MEF during pneumococcal otitis media, and future studies will need to define the contribution of these products to acute and chronic middle ear tissue injury. PMID:1657782

  9. Chinchilla middle-ear admittance and sound power: High-frequency estimates and effects of inner-ear modifications

    PubMed Central

    Ravicz, Michael E.; Rosowski, John J.

    2012-01-01

    The middle-ear input admittance relates sound power into the middle ear (ME) and sound pressure at the tympanic membrane (TM). ME input admittance was measured in the chinchilla ear canal as part of a larger study of sound power transmission through the ME into the inner ear. The middle ear was open, and the inner ear was intact or modified with small sensors inserted into the vestibule near the cochlear base. A simple model of the chinchilla ear canal, based on ear canal sound pressure measurements at two points along the canal and an assumption of plane-wave propagation, enables reliable estimates of YTM, the ME input admittance at the TM, from the admittance measured relatively far from the TM. YTM appears valid at frequencies as high as 17 kHz, a much higher frequency than previously reported. The real part of YTM decreases with frequency above 2 kHz. Effects of the inner-ear sensors (necessary for inner ear power computation) were small and generally limited to frequencies below 3 kHz. Computed power reflectance was ∼0.1 below 3.5 kHz, lower than with an intact ME below 2.5 kHz, and nearly 1 above 16 kHz. PMID:23039439

  10. Extracellular and intracellular melanin in inflammatory middle ear disease.

    PubMed

    Fritz, Mark A; Roehm, Pamela C; Bannan, Michael A; Lalwani, Anil K

    2014-06-01

    Melanin is a pigmented polymer with a known role in dermal solar protection. In vertebrates, melanogenesis has been reported in leukocyte populations, suggesting a potential role in innate immunity. In this study, we report the novel finding of melanin associated with chronic inflammation and speculate on its potential role in the middle ear and mastoid. Retrospective review of case series. Medical records of six patients who demonstrated melanin in the ear were reviewed. Six patients from 1 to 63 years of age were identified with extracellular melanin and melanin-laden histiocytes within the middle ear and/or mastoid air cells at time of surgery. Concurrent intraoperative findings included cholesteatoma (n = 3), chronic suppurative otitis media (n = 2), and coalescent mastoiditis (n = 1). Histologically, extracellular melanin and melanin-laden histiocytes were identified by Fontana-Masson stain; absence of melanocytes was confirmed by the absence of Melan-A staining. One patient had a positive stain for CD163 (a marker for macrophages). This case series is the first demonstration of melanin within middle ear mucosa without melanocytes in immediate proximity or metastatic melanocytic lesions. Melanin's presence in the setting of inflammation suggests that there may be a heretofore unreported link between the pigmentary and immune systems in the middle ear. 4.

  11. Carbachol induces TGF-alpha expression and colonic epithelial cell proliferation in sensory-desensitised rats.

    PubMed

    Bulut, Kerem; Felderbauer, Peter; Hoeck, Karoline; Schmidt, Wolfgang E; Hoffmann, Peter

    2010-03-01

    Signals for the expression of the peptide growth factors epidermal growth factor and transforming growth factor-alpha (TGFalpha) in the gastrointestinal mucosa are largely unknown. We have shown earlier that extrinsic afferents in the gastrointestinal tract induce TGFalpha expression in colonic mucosa via the deliberation of neurotransmitters substance P and calcitonin gene-related peptide. The aim of our present study was to determine the effects of carbachol on mucosal TGFalpha expression and epithelial cell proliferation in vivo. Rats were divided in three groups. Group 1 was treated with vehicle only, group 2 received one single subcutaneous injection of 250 microg/kg of carbachol and animals in group 3 were sensory-desensitised prior to the injection of 250 microg/kg carbachol. TGFalpha expression and epithelial cell proliferation was evaluated by polymerase chain reaction, Western blot analysis and bromodeoxyuridine staining. Carbachol induced a significant increase in mucosal epithelial cell proliferation and TGFalpha expression. Sensory desensitisation did neither abolish the increased TGFalpha expression nor the increase in epithelial cell proliferation. Parasympathetic pathways are involved in the control of TGFalpha expression in gastrointestinal mucosa as well as in epithelial cell proliferation.

  12. Reactivity of Acetylcholine Esterase in inner Ear Maculae of Fish after Development at Hypergravity

    NASA Astrophysics Data System (ADS)

    Feucht, I.; Hilbig, R.; Anken, R.

    It has been shown earlier that the growth of inner ear otoliths of larval fish is (among other environmental factors) guided by the gravity vector. This guidance most probably is effected by the efferent vestibular system in the brainstem, because a transection of the nervus vestibularis has been shown to effect a cessation of the supply of calcium to the otoliths. The efferent innervation of fish inner ear maculae uses the synaptic transmitter acetylcholine (ACh). Therefore, we were - in order to further assess the role of the efferent system for otolith growth - prompted to determine ACh esterase-reactivity in the sensory epithelium of the utricle and the saccule (as well as in a non-gravity relevant brain region for control) in larval cichlid fish (Oreochromis mossambicus), which had been maintained at hypergravity during their development. The respective data will be communicated at the meeting. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 9997).

  13. Influence of Sensory Dependence on Postural Control

    NASA Technical Reports Server (NTRS)

    Santana, Patricia A.; Mulavara, Ajitkumar P.; Fiedler, Matthew J.

    2011-01-01

    The current project is part of an NSBRI funded project, "Development of Countermeasures to Aid Functional Egress from the Crew Exploration Vehicle Following Long-Duration Spaceflight." The development of this countermeasure is based on the use of imperceptible levels of electrical stimulation to the balance organs of the inner ear to assist and enhance the response of a person s sensorimotor function. These countermeasures could be used to increase an astronaut s re-adaptation rate to Earth s gravity following long-duration space flight. The focus of my project is to evaluate and examine the correlation of sensory preferences for vision and vestibular systems. Disruption of the sensorimotor functions following space flight affects posture, locomotion and spatial orientation tasks in astronauts. The Group Embedded Figures Test (GEFT), the Rod and Frame Test (RFT) and the Computerized Dynamic Posturography Test (CDP) are measurements used to examine subjects visual and vestibular sensory preferences. The analysis of data from these tasks will assist in relating the visual dependence measures recognized in the GEFT and RFT with vestibular dependence measures recognized in the stability measures obtained during CDP. Studying the impact of sensory dependence on the performance in varied tasks will help in the development of targeted countermeasures to help astronauts readapt to gravitational changes after long duration space flight.

  14. Self-ear cleaning practices and the associated risk of ear injuries and ear-related symptoms in a group of university students.

    PubMed

    Khan, Nasim Banu; Thaver, Sivashnee; Govender, Samantha Marlene

    2017-12-31

    Self-ear cleaning is the insertion of objects into the ear canal to clean it, a widespread practice that has the potential to compromise its integrity as a natural, selfcleansing mechanism, and a risk factor for possible injuries. The practice is common among young adults and highest in university than any other graduates. This study aimed to determine the self-ear cleaning practices and associated risk of injury and related symptoms in undergraduate students at KwaZulu-Natal University. The descriptive survey utilized a self-administered questionnaire. Of the 206 participants that responded, 98% engaged in self-ear cleaning, with 75% indicating that it was beneficial. The commonest method (79.6%) being the use of cotton buds, with an associated injury rate of 2.4%. There was no statistically significant associations between those who used or did not use cotton buds and the symptoms experienced. The complications indicate that self-ear cleaning does pose a risk for injury, necessitating more community information and education.

  15. TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear.

    PubMed

    Pan, Bifeng; Géléoc, Gwenaelle S; Asai, Yukako; Horwitz, Geoffrey C; Kurima, Kiyoto; Ishikawa, Kotaro; Kawashima, Yoshiyuki; Griffith, Andrew J; Holt, Jeffrey R

    2013-08-07

    Sensory transduction in auditory and vestibular hair cells requires expression of transmembrane channel-like (Tmc) 1 and 2 genes, but the function of these genes is unknown. To investigate the hypothesis that TMC1 and TMC2 proteins are components of the mechanosensitive ion channels that convert mechanical information into electrical signals, we recorded whole-cell and single-channel currents from mouse hair cells that expressed Tmc1, Tmc2, or mutant Tmc1. Cells that expressed Tmc2 had high calcium permeability and large single-channel currents, while cells with mutant Tmc1 had reduced calcium permeability and reduced single-channel currents. Cells that expressed Tmc1 and Tmc2 had a broad range of single-channel currents, suggesting multiple heteromeric assemblies of TMC subunits. The data demonstrate TMC1 and TMC2 are components of hair cell transduction channels and contribute to permeation properties. Gradients in TMC channel composition may also contribute to variation in sensory transduction along the tonotopic axis of the mammalian cochlea. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Identification and characterization of mouse otic sensory lineage genes

    PubMed Central

    Hartman, Byron H.; Durruthy-Durruthy, Robert; Laske, Roman D.; Losorelli, Steven; Heller, Stefan

    2015-01-01

    Vertebrate embryogenesis gives rise to all cell types of an organism through the development of many unique lineages derived from the three primordial germ layers. The otic sensory lineage arises from the otic vesicle, a structure formed through invagination of placodal non-neural ectoderm. This developmental lineage possesses unique differentiation potential, giving rise to otic sensory cell populations including hair cells, supporting cells, and ganglion neurons of the auditory and vestibular organs. Here we present a systematic approach to identify transcriptional features that distinguish the otic sensory lineage (from early otic progenitors to otic sensory populations) from other major lineages of vertebrate development. We used a microarray approach to analyze otic sensory lineage populations including microdissected otic vesicles (embryonic day 10.5) as well as isolated neonatal cochlear hair cells and supporting cells at postnatal day 3. Non-otic tissue samples including periotic tissues and whole embryos with otic regions removed were used as reference populations to evaluate otic specificity. Otic populations shared transcriptome-wide correlations in expression profiles that distinguish members of this lineage from non-otic populations. We further analyzed the microarray data using comparative and dimension reduction methods to identify individual genes that are specifically expressed in the otic sensory lineage. This analysis identified and ranked top otic sensory lineage-specific transcripts including Fbxo2, Col9a2, and Oc90, and additional novel otic lineage markers. To validate these results we performed expression analysis on select genes using immunohistochemistry and in situ hybridization. Fbxo2 showed the most striking pattern of specificity to the otic sensory lineage, including robust expression in the early otic vesicle and sustained expression in prosensory progenitors and auditory and vestibular hair cells and supporting cells. PMID:25852475

  17. Theory of forward and reverse middle-ear transmission applied to otoacoustic emissions in infant and adult ears

    PubMed Central

    Keefe, Douglas H.; Abdala, Carolina

    2008-01-01

    The purpose of this study is to understand why otoacoustic emission (OAE) levels are higher in normal-hearing human infants relative to adults. In a previous study, distortion product (DP) OAE input/output (I/O) functions were shown to differ at f2=6 kHz in adults compared to infants through 6 months of age. These DPOAE I/O functions were used to noninvasively assess immaturities in forward/reverse transmission through the ear canal and middle ear [Abdala, C., and Keefe, D. H., (2006). J. Acoust Soc. Am. 120, 3832–3842]. In the present study, ear-canal reflectance and DPOAEs measured in the same ears were analyzed using a scattering-matrix model of forward and reverse transmission in the ear canal, middle ear, and cochlea. Reflectance measurements were sensitive to frequency-dependent effects of ear-canal and middle-ear transmission that differed across OAE type and subject age. Results indicated that DPOAE levels were larger in infants mainly because the reverse middle-ear transmittance level varied with ear-canal area, which differed by more than a factor of 7 between term infants and adults. The forward middle-ear transmittance level was −16 dB less in infants, so that the conductive efficiency was poorer in infants than adults. PMID:17348521

  18. Altered Expression of Middle and Inner Ear Cytokines in Mouse Otitis Media

    PubMed Central

    MacArthur, Carol J.; Pillers, De-Ann M.; Pang, Jiaqing; Kempton, J. Beth; Trune, Dennis R.

    2010-01-01

    Objectives/Hypothesis The inner ear is at risk for sensorineural hearing loss in both acute and chronic otitis media (OM), but the underlying mechanisms underlying sensorineural hearing loss are unknown. Previous gene expression array studies showed cytokine genes might be upregulated in the cochleas of mice with acute and chronic otitis media. This implies that the inner ear could manifest a direct inflammatory response to OM that may cause sensorineural damage. Therefore, to better understand inner ear cytokine gene expression during OM, quantitative RT-PCR and immunohistochemistry were performed on mouse models to evaluate middle and inner ear inflammatory and remodeling cytokines. Study Design Basic science experiment. Methods An acute OM model was created in Balb/c mice by a transtympanic injection of S. pneumoniae in one ear; the other ear used as a control. C3H/HeJ mice were screened for unilateral chronic OM with the non-infected ear serving as control. Results Both acute and chronic OM caused both the middle ear and inner tissues in these two mouse models to over express numerous cytokine genes related to tissue remodeling (TNFα, FGF, BMP) and angiogenesis (VEGF), as well as inflammatory cell proliferation (IL-1α,β, IL-2, IL-6). Immunohistochemistry confirmed that both the middle ear and inner ear tissues expressed these cytokines. Conclusion Cochlear tissues are capable of expressing cytokine mRNA that contributes to the inflammation and remodeling that occur in association with middle ear disease. This provides a potential molecular basis for the transient and permanent sensorineural hearing loss often reported with acute and chronic OM. Level of Evidence N/A PMID:21271590

  19. Red ear syndrome.

    PubMed

    Purdy, R Allan; Dodick, David W

    2007-08-01

    The red ear syndrome is a rare syndrome originally described by Lance in 1994. It involves pain in and around the ear and associated autonomic phenomena, the most significant of which is cutaneous erythema of the ear ipsilateral to the pain and obvious to the patient and examiner during the attack. It may well represent an auriculo-autonomic cephalgia and/or be part of the group of disorders recognized as trigeminal autonomic cephalalgias. As a syndrome, it still lacks specificity in regard to etiology, mechanisms, and treatment but is important to recognize clinically because of its associations.

  20. Long-term consequences of Sox9 depletion on inner ear development

    PubMed Central

    Park, Byung-Yong; Saint-Jeannet, Jean-Pierre

    2010-01-01

    The transcription factor Sox9 has been implicated in inner ear formation in several species. To investigate the long-term consequences of Sox9 depletion on inner ear development we analyzed the inner ear architecture of Sox9-depleted Xenopus tadpoles generated by injection of increasing amounts of Sox9 morpholino antisense oligonucleotides. We found that Sox9-depletion resulted in major defects in the development of vestibular structures, semicircular canals and utricle, while the ventrally located saccule was less severely affected in these embryos. Consistent with this phenotype we observed a specific loss of the dorsal expression of Wnt3a expression in the otic vesicle of Sox9 morphants, associated with an increase in cell death and a reduction in cell proliferation in the region of the presumptive otic epithelium. We propose that in addition to its early role in placode specification, Sox9 is also required for the maintenance of progenitors in the otic epithelium. PMID:20201105

  1. Could ionizing radiation forestall cauliflower ear?

    PubMed

    Hwang, K; Kim, C W; Lee, S I; Park, I S; Kim, W C; Loh, J J

    2001-02-01

    Repeated trauma to the ear very often results in "cauliflower ear." Many methods have been suggested to prevent an injured ear from demonstrating a cauliflowerlike deformity. The principles of treatment are evacuation of the hematoma, control of the reaccumulation of fluid, and maintenance of the cartilage contour. The authors studied the effect of ionizing radiation on deformed rabbit ears induced by repeated trauma. Twenty ears (10 rabbits) were used in the experiment. The animals were divided into four groups (control, preradiation, low dose, and high dose). Hematoma was produced by pounding the lateral side of the auricle 10 times with a 50-g weight at a height of 15 cm. The thickness of the injured and uninjured sites was measured, and histological analysis was performed for each group. The thickness of the ears of the irradiated groups was significantly less than the control group. The authors think that radiation treatment of repeatedly injured ears could prevent ear deformity, and could possibly be an adjunctive form of management of cauliflower ear in addition to hematoma evacuation and compression therapy.

  2. Ear tube insertion

    MedlinePlus

    ... eardrum may cause some hearing loss. But most children do not have long-term damage to their hearing or speech, even when the ... not go away with treatment, or if a child has many ear infections ... or that damages nearby nerves Injury to the ear after sudden ...

  3. Effects of NSAIDs on the Inner Ear: Possible Involvement in Cochlear Protection

    PubMed Central

    Hoshino, Tomofumi; Tabuchi, Keiji; Hara, Akira

    2010-01-01

    Cyclooxygenase and lipoxygenase, two important enzymes involved in arachidonic acid metabolism, are major targets of non-steroidal anti-inflammatory drugs (NSAIDs). Recent investigations suggest that arachidonic cascades and their metabolites may be involved in maintaining inner ear functions. The excessive use of aspirin may cause tinnitus in humans and impairment of the outer hair cell functions in experimental animals. On the other hand, NSAIDs reportedly exhibit protective effects against various kinds of inner ear disorder. The present review summarizes the effects of NSAIDs on cochlear pathophysiology. NSAIDs are a useful ameliorative adjunct in the management of inner ear disorders. PMID:27713301

  4. Fractalkine Signaling Regulates Macrophage Recruitment into the Cochlea and Promotes the Survival of Spiral Ganglion Neurons after Selective Hair Cell Lesion.

    PubMed

    Kaur, Tejbeer; Zamani, Darius; Tong, Ling; Rubel, Edwin W; Ohlemiller, Kevin K; Hirose, Keiko; Warchol, Mark E

    2015-11-11

    Macrophages are recruited into the cochlea in response to injury caused by acoustic trauma or ototoxicity, but the nature of the interaction between macrophages and the sensory structures of the inner ear remains unclear. The present study examined the role of fractalkine signaling in regulating the injury-evoked behavior of macrophages following the selective ablation of cochlear hair cells. We used a novel transgenic mouse model in which the human diphtheria toxin receptor (huDTR) is selectively expressed under the control of Pou4f3, a hair cell-specific transcription factor. Administration of diphtheria toxin (DT) to these mice resulted in nearly complete ablation of cochlear hair cells, with no evident pathology among supporting cells, spiral ganglion neurons, or cells of the cochlear lateral wall. Hair cell death led to an increase in macrophages associated with the sensory epithelium of the cochlea. Their numbers peaked at 14 days after DT and then declined at later survival times. Increased macrophages were also observed within the spiral ganglion, but their numbers remained elevated for (at least) 56 d after DT. To investigate the role of fractalkine signaling in macrophage recruitment, we crossed huDTR mice to a mouse line that lacks expression of the fractalkine receptor (CX3CR1). Disruption of fractalkine signaling reduced macrophage recruitment into both the sensory epithelium and spiral ganglion and also resulted in diminished survival of spiral ganglion neurons after hair cell death. Our results suggest a fractalkine-mediated interaction between macrophages and the neurons of the cochlea. It is known that damage to the inner ear leads to recruitment of inflammatory cells (macrophages), but the chemical signals that initiate this recruitment and the functions of macrophages in the damaged ear are unclear. Here we show that fractalkine signaling regulates macrophage recruitment into the cochlea and also promotes the survival of cochlear afferents after

  5. Streptomycin action to the mammalian inner ear vestibular organs: comparison between pigmented guinea pigs and rats.

    PubMed

    Meza, Graciela; Aguilar-Maldonado, Beatriz

    2007-01-01

    Streptomycin is the antibiotic of choice to treat tuberculosis and other infectious diseases but it causes vestibular malfunction and hipoacusia. Rodents are usually employed as models of drug action to the inner ear and results are extrapolated to what happens in humans. In rats, streptomycin destroys macular sensory cells and does not affect cochlear ones, whereas in guinea pigs the contrary is true. Action on the vestibular cristae cells involved in vestibulo-ocular reflex integrity is less clear. Thus, we compared this response in both pigmented guinea pigs (Cavia cobaya) and rats (Rattus norvegicus) after parallel streptomycin chronic treatment. In guinea pigs, the reflex was obliterated along treatment time; in rats this behavior was not observed, suggesting that the end organ target was diverse. In recent studies, streptidine, a streptomycin derivative found in the blood of humans and rats treated with streptomycin, was the actual ototoxic agent. The putative streptomycin vestibular organ target observed in humans corresponds with the guinea pig observations. Results observed in rats are controversial: streptidine did not cause any damage either to vestibular cristae nor auditory cells. We hypothesize differential drug metabolism and distribution and conclude that results in laboratory animals may not always be applicable in the human situation.

  6. Involvement of p53 and Bcl-2 in sensory cell degeneration in aging rat cochleae.

    PubMed

    Xu, Yang; Yang, Wei Ping; Hu, Bo Hua; Yang, Shiming; Henderson, Donald

    2017-06-01

    p53 and Bcl-2 (B-cell lymphoma 2) are involved in the process of sensory cell degeneration in aging cochleae. To determine molecular players in age-related hair cell degeneration, this study examined the changes in p53 and Bcl-2 expression at different stages of apoptotic and necrotic death of hair cells in aging rat cochleae. Young (3-4 months) and aging (23-24 months) Fisher 344/NHsd rats were used. The thresholds of the auditory brainstem response (ABR) were measured to determine the auditory function. Immunolabeling was performed to determine the expression of p53 and Bcl-2 proteins in the sensory epithelium. Propidium iodide staining was performed to determine the morphologic changes in hair cell nuclei. Aging rats exhibited a significant elevation in ABR thresholds at all tested frequencies (p < 0.001). The p53 and Bcl-2 immunoreactivity was increased in aging hair cells showing the early signs of apoptotic changes in their nuclei. The Bcl-2 expression increase was also observed in hair cells displaying early signs of necrosis. As the hair cell degenerative process advanced, p53 and Bcl-2 immunoreactivity became reduced or absent. In the areas where no detectable nuclear staining was present, p53 and Bcl-2 immunoreactivity was absent.

  7. Perfusion-decellularization of human ear grafts enables ECM-based scaffolds for auricular vascularized composite tissue engineering.

    PubMed

    Duisit, Jérôme; Amiel, Hadrien; Wüthrich, Tsering; Taddeo, Adriano; Dedriche, Adeline; Destoop, Vincent; Pardoen, Thomas; Bouzin, Caroline; Joris, Virginie; Magee, Derek; Vögelin, Esther; Harriman, David; Dessy, Chantal; Orlando, Giuseppe; Behets, Catherine; Rieben, Robert; Gianello, Pierre; Lengelé, Benoît

    2018-06-01

    Human ear reconstruction is recognized as the emblematic enterprise in tissue engineering. Up to now, it has failed to reach human applications requiring appropriate tissue complexity along with an accessible vascular tree. We hereby propose a new method to process human auricles in order to provide a poorly immunogenic, complex and vascularized ear graft scaffold. 12 human ears with their vascular pedicles were procured. Perfusion-decellularization was applied using a SDS/polar solvent protocol. Cell and antigen removal was examined by histology and DNA was quantified. Preservation of the extracellular matrix (ECM) was assessed by conventional and 3D-histology, proteins and cytokines quantifications. Biocompatibility was assessed by implantation in rats for up to 60 days. Adipose-derived stem cells seeding was conducted on scaffold samples and with human aortic endothelial cells whole graft seeding in a perfusion-bioreactor. Histology confirmed cell and antigen clearance. DNA reduction was 97.3%. ECM structure and composition were preserved. Implanted scaffolds were tolerated in vivo, with acceptable inflammation, remodeling, and anti-donor antibody formation. Seeding experiments demonstrated cell engraftment and viability. Vascularized and complex auricular scaffolds can be obtained from human source to provide a platform for further functional auricular tissue engineered constructs, hence providing an ideal road to the vascularized composite tissue engineering approach. The ear is emblematic in the biofabrication of tissues and organs. Current regenerative medicine strategies, with matrix from donor tissues or 3D-printed, didn't reach any application for reconstruction, because critically missing a vascular tree for perfusion and transplantation. We previously described the production of vascularized and cell-compatible scaffolds, from porcine ear grafts. In this study, we ---- applied findings directly to human auricles harvested from postmortem donors

  8. Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells.

    PubMed

    White, Patricia M; Doetzlhofer, Angelika; Lee, Yun Shain; Groves, Andrew K; Segil, Neil

    2006-06-22

    Sensory hair cells of the mammalian organ of Corti in the inner ear do not regenerate when lost as a consequence of injury, disease, or age-related deafness. This contrasts with other vertebrates such as birds, where the death of hair cells causes surrounding supporting cells to re-enter the cell cycle and give rise to both new hair cells and supporting cells. It is not clear whether the lack of mammalian hair cell regeneration is due to an intrinsic inability of supporting cells to divide and differentiate or to an absence or blockade of regenerative signals. Here we show that post-mitotic supporting cells purified from the postnatal mouse cochlea retain the ability to divide and trans-differentiate into new hair cells in culture. Furthermore, we show that age-dependent changes in supporting cell proliferative capacity are due in part to changes in the ability to downregulate the cyclin-dependent kinase inhibitor p27(Kip1) (also known as Cdkn1b). These results indicate that postnatal mammalian supporting cells are potential targets for therapeutic manipulation.

  9. Anomalies of the middle and inner ear.

    PubMed

    Rodriguez, Kimsey; Shah, Rahul K; Kenna, Margaret

    2007-02-01

    The development of the middle and inner ear highlights the intricacy of embryology. As early as 3 weeks after fertilization, the inner ear begins taking form. This process, along with development of the middle ear, continues throughout gestation. At birth, the middle ear, inner ear, and associated structures are almost adult size. An understanding of the embryologic development of the ear serves as a foundation for evaluating and managing congenital malformations of these structures. The focus of this article is the normal, abnormal, and arrested development of the middle and inner ear, with a clinical emphasis on malformed middle and inner ear structures and a discussion of associated syndromes.

  10. Non-neural ectoderm is really neural: evolution of developmental patterning mechanisms in the non-neural ectoderm of chordates and the problem of sensory cell homologies.

    PubMed

    Holland, Linda Z

    2005-07-15

    In chordates, the ectoderm is divided into the neuroectoderm and the so-called non-neural ectoderm. In spite of its name, however, the non-neural ectoderm contains numerous sensory cells. Therefore, the term "non-neural" ectoderm should be replaced by "general ectoderm." At least in amphioxus and tunicates and possibly in vertebrates as well, both the neuroectoderm and the general ectoderm are patterned anterior/posteriorly by mechanisms involving retinoic acid and Hox genes. In amphioxus and tunicates the ectodermal sensory cells, which have a wide range of ciliary and microvillar configurations, are mostly primary neurons sending axons to the CNS, although a minority lack axons. In contrast, vertebrate mechanosensory cells, called hair cells, are all secondary neurons that lack axons and have a characteristic eccentric cilium adjacent to a group of microvilli of graded lengths. It has been highly controversial whether the ectodermal sensory cells in the oral siphons of adult tunicates are homologous to vertebrate hair cells. In some species of tunicates, these cells appear to be secondary neurons, and microvillar and ciliary configurations of some of these cells approach those of vertebrate hair cells. However, none of the tunicate cells has all the characteristics of a hair cell, and there is a high degree of variation among ectodermal sensory cells within and between different species. Thus, similarities between the ectodermal sensory cells of any one species of tunicate and craniate hair cells may well represent convergent evolution rather than homology. Copyright 2005 Wiley-Liss, Inc.

  11. Laterality and unilateral deafness: Patients with congenital right ear deafness do not develop atypical language dominance.

    PubMed

    Van der Haegen, Lise; Acke, Frederic; Vingerhoets, Guy; Dhooge, Ingeborg; De Leenheer, Els; Cai, Qing; Brysbaert, Marc

    2016-12-01

    Auditory speech perception, speech production and reading lateralize to the left hemisphere in the majority of healthy right-handers. In this study, we investigated to what extent sensory input underlies the side of language dominance. We measured the lateralization of the three core subprocesses of language in patients who had profound hearing loss in the right ear from birth and in matched control subjects. They took part in a semantic decision listening task involving speech and sound stimuli (auditory perception), a word generation task (speech production) and a passive reading task (reading). The results show that a lack of sensory auditory input on the right side, which is strongly connected to the contralateral left hemisphere, does not lead to atypical lateralization of speech perception. Speech production and reading were also typically left lateralized in all but one patient, contradicting previous small scale studies. Other factors such as genetic constraints presumably overrule the role of sensory input in the development of (a)typical language lateralization. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Structure and function of the mammalian middle ear. I: Large middle ears in small desert mammals.

    PubMed

    Mason, Matthew J

    2016-02-01

    Many species of small desert mammals are known to have expanded auditory bullae. The ears of gerbils and heteromyids have been well described, but much less is known about the middle ear anatomy of other desert mammals. In this study, the middle ears of three gerbils (Meriones, Desmodillus and Gerbillurus), two jerboas (Jaculus) and two sengis (elephant-shrews: Macroscelides and Elephantulus) were examined and compared, using micro-computed tomography and light microscopy. Middle ear cavity expansion has occurred in members of all three groups, apparently in association with an essentially 'freely mobile' ossicular morphology and the development of bony tubes for the middle ear arteries. Cavity expansion can occur in different ways, resulting in different subcavity patterns even between different species of gerbils. Having enlarged middle ear cavities aids low-frequency audition, and several adaptive advantages of low-frequency hearing to small desert mammals have been proposed. However, while Macroscelides was found here to have middle ear cavities so large that together they exceed brain volume, the bullae of Elephantulus are considerably smaller. Why middle ear cavities are enlarged in some desert species but not others remains unclear, but it may relate to microhabitat. © 2015 Anatomical Society.

  13. Round window administration of gentamicin: a new method for the study of ototoxicity of cochlear hair cells.

    PubMed

    Husmann, K R; Morgan, A S; Girod, D A; Durham, D

    1998-11-01

    Damage to inner ear sensory hair cells after systemic administration of ototoxic drugs has been documented in humans and animals. Birds have the ability to regenerate new hair cells to replace those damaged by drugs or noise. Unfortunately, the systemic administration of gentamicin damages both ears in a variable fashion with potentially confounding systemic drug effects. We developed a method of direct application of gentamicin to one cochlea of hatchling chickens, allowing the other ear to serve as a within-animal control. We tested variables including the vehicle for application, location of application, dosage, and duration of gentamicin exposure. After 5 or 28 days survival, the percent length damage to the cochlea and regeneration of hair cells was evaluated using scanning electron microscopy. Controls consisted of the opposite unexposed cochlea and additional animals which received saline instead of gentamicin. Excellent damage was achieved using gentamicin-soaked Gelfoam pledgets applied to the round window membrane. The percent length damage could be varied from 15 to 100% by changing the dosage of gentamicin, with exposures as short as 30 min. No damage was observed in control animals. Regeneration of hair cells was observed in both the base and apex by 28 days survival.

  14. [Effect size on resonance of the outer ear canal by simulation of middle ear lesions using a temporal bone preparation].

    PubMed

    Scheinpflug, L; Vorwerk, U; Begall, K

    1995-01-01

    By means of a model of the external and the middle ear it is possible to simulate various, exactly defined pathological conditions of the middle ear and to describe their influence on ear canal resonance. Starting point of the investigations are fresh postmortem preparations of 8 human temporal bones with an intact ear drum and a retained skin of the ear canal. The compliance of the middle ear does not significantly differ from the clinical data of probands with healthy ears. After antrotomy it is possible to simulate pathological conditions of the middle ear one after the other at the same temporal bone. The influence of the changed middle ear conditions on ear drum compliance, ear canal volume and on the resonance curve of the external ear canal was investigated. For example, the middle ear was filled with water to create approximately the same conditions as in acute serous otitis media. In this middle ear condition a significant increase of the sound pressure amplification was found, on an average by 4 decibels compared to the unchanged temporal bone model. A small increase in resonance frequency was also measured. The advantages of this model are the approximately physiological conditions and the constant dimensions of the external and middle ear.

  15. Surgical correction of cauliflower ear.

    PubMed

    Yotsuyanagi, T; Yamashita, K; Urushidate, S; Yokoi, K; Sawada, Y; Miyazaki, S

    2002-07-01

    We have classified the cauliflower ear into different types according to the zone and the degree of deformity. One major group is deformity without change in the outline of the ear, and this is divided into four subgroups according to the zone. All of these subgroups can be treated by shaving the deformed cartilage through suitable incision lines. For deformities accompanied by a skin deficit, a postauricular skin flap should be used. The other major group is deformity accompanied by a change in the outline of the ear, which is divided into two subgroups. If the ear is rigid, a conchal cartilage graft is used. If the structural integrity of the ear is poor, costal cartilage is used to provide rigidity.

  16. Inner ear changes in mucopolysaccharidosis type I/Hurler syndrome.

    PubMed

    Kariya, Shin; Schachern, Patricia A; Nishizaki, Kazunori; Paparella, Michael M; Cureoglu, Sebahattin

    2012-10-01

    Mucopolysaccharidosis type I/Hurler syndrome is an autosomal recessive disease caused by a deficiency of α-L-iduronidase activity. Recurrent middle ear infections and hearing loss are common complications in Hurler syndrome. Although sensorineural and conductive components occur, the mechanism of sensorineural hearing loss has not been determined. The purpose of this study is to evaluate the quantitative inner ear histopathology of the temporal bones of patients with Hurler syndrome. Eleven temporal bones from 6 patients with Hurler syndrome were examined. Age-matched healthy control samples consisted of 14 temporal bones from 7 cases. Temporal bones were serially sectioned in the horizontal plane and stained with hematoxylin and eosin. The number of spiral ganglion cells, loss of cochlear hair cells, area of stria vascularis, and cell density of spiral ligament were evaluated using light microscopy. There was no significant difference between Hurler syndrome and healthy controls in the number of spiral ganglion cells, area of stria vascularis, or cell density of spiral ligament. The number of cochlear hair cells in Hurler syndrome was significantly decreased compared with healthy controls. Auditory pathophysiology in the central nerve system in Hurler syndrome remains unknown; however, decreased cochlear hair cells may be one of the important factors for the sensorineural component of hearing loss.

  17. Sensory conflict in motion sickness: An observer theory approach

    NASA Technical Reports Server (NTRS)

    Oman, Charles M.

    1989-01-01

    Motion sickness is the general term describing a group of common nausea syndromes originally attributed to motion-induced cerebral ischemia, stimulation of abdominal organ afferent, or overstimulation of the vestibular organs of the inner ear. Sea-, car-, and airsicknesses are the most commonly experienced examples. However, the discovery of other variants such as Cinerama-, flight simulator-, spectacle-, and space sickness in which the physical motion of the head and body is normal or absent has led to a succession of sensory conflict theories which offer a more comprehensive etiologic perspective. Implicit in the conflict theory is the hypothesis that neutral and/or humoral signals originate in regions of the brain subversing spatial orientation, and that these signals somehow traverse to other centers mediating sickness symptoms. Unfortunately, the present understanding of the neurophysiological basis of motion sickness is far from complete. No sensory conflict neuron or process has yet been physiologically identified. To what extent can the existing theory be reconciled with current knowledge of the physiology and pharmacology of nausea and vomiting. The stimuli which causes sickness, synthesizes a contemporary Observer Theory view of the Sensory Conflict hypothesis are reviewed, and a revised model for the dynamic coupling between the putative conflict signals and nausea magnitude estimates is presented. The use of quantitative models for sensory conflict offers a possible new approach to improving the design of visual and motion systems for flight simulators and other virtual environment display systems.

  18. Multiple conserved cell adhesion protein interactions mediate neural wiring of a sensory circuit in C. elegans.

    PubMed

    Kim, Byunghyuk; Emmons, Scott W

    2017-09-13

    Nervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity in C. elegans , we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male. Two interacting pairs of cell surface proteins independently promote fasciculation between sensory neuron HOA and its postsynaptic target interneuron AVG: BAM-2/neurexin-related in HOA binds to CASY-1/calsyntenin in AVG; SAX-7/L1CAM in sensory neuron PHC binds to RIG-6/contactin in AVG. A third, basal pathway results in considerable HOA-AVG fasciculation and synapse formation in the absence of the other two. The features of this multiplexed mechanism help to explain how complex connectivity is encoded and robustly established during nervous system development.

  19. The L1-type cell adhesion molecule Neuroglian is necessary for maintenance of sensory axon advance in the Drosophila embryo.

    PubMed

    Martin, Veronica; Mrkusich, Eli; Steinel, Martin C; Rice, Jason; Merritt, David J; Whitington, Paul M

    2008-04-08

    Cell adhesion molecules have long been implicated in the regulation of axon growth, but the precise cellular roles played by individual cell adhesion molecules and the molecular basis for their action are still not well understood. We have used the sensory system of the Drosophila embryo to shed light on the mechanism by which the L1-type cell adhesion molecule Neuroglian regulates axon growth. We have found a highly penetrant sensory axon stalling phenotype in neuroglian mutant embryos. Axons stalled at a variety of positions along their normal trajectory, but most commonly in the periphery some distance along the peripheral nerve. All lateral and dorsal cluster sensory neurons examined, except for the dorsal cluster neuron dbd, showed stalling. Sensory axons were never seen to project along inappropriate pathways in neuroglian mutants and stalled axons showed normal patterns of fasciculation within nerves. The growth cones of stalled axons possessed a simple morphology, similar to their appearance in wild-type embryos when advancing along nerves. Driving expression of the wild-type form of Neuroglian in sensory neurons alone rescued the neuroglian mutant phenotype of both pioneering and follower neurons. A partial rescue was achieved by expressing the Neuroglian extracellular domain. Over/mis-expression of Neuroglian in all neurons, oenocytes or trachea had no apparent effect on sensory axon growth. We conclude that Neuroglian is necessary to maintain axon advance along axonal substrates, but is not required for initiation of axon outgrowth, axon fasciculation or recognition of correct growth substrates. Expression of Neuroglian in sensory neurons alone is sufficient to promote axon advance and the intracellular region of the molecule is largely dispensable for this function. It is unlikely, therefore, that Nrg acts as a molecular 'clutch' to couple adhesion of F-actin within the growth cone to the extracellular substrate. Rather, we suggest that Neuroglian

  20. The L1-type cell adhesion molecule Neuroglian is necessary for maintenance of sensory axon advance in the Drosophila embryo

    PubMed Central

    Martin, Veronica; Mrkusich, Eli; Steinel, Martin C; Rice, Jason; Merritt, David J; Whitington, Paul M

    2008-01-01

    Background Cell adhesion molecules have long been implicated in the regulation of axon growth, but the precise cellular roles played by individual cell adhesion molecules and the molecular basis for their action are still not well understood. We have used the sensory system of the Drosophila embryo to shed light on the mechanism by which the L1-type cell adhesion molecule Neuroglian regulates axon growth. Results We have found a highly penetrant sensory axon stalling phenotype in neuroglian mutant embryos. Axons stalled at a variety of positions along their normal trajectory, but most commonly in the periphery some distance along the peripheral nerve. All lateral and dorsal cluster sensory neurons examined, except for the dorsal cluster neuron dbd, showed stalling. Sensory axons were never seen to project along inappropriate pathways in neuroglian mutants and stalled axons showed normal patterns of fasciculation within nerves. The growth cones of stalled axons possessed a simple morphology, similar to their appearance in wild-type embryos when advancing along nerves. Driving expression of the wild-type form of Neuroglian in sensory neurons alone rescued the neuroglian mutant phenotype of both pioneering and follower neurons. A partial rescue was achieved by expressing the Neuroglian extracellular domain. Over/mis-expression of Neuroglian in all neurons, oenocytes or trachea had no apparent effect on sensory axon growth. Conclusion We conclude that Neuroglian is necessary to maintain axon advance along axonal substrates, but is not required for initiation of axon outgrowth, axon fasciculation or recognition of correct growth substrates. Expression of Neuroglian in sensory neurons alone is sufficient to promote axon advance and the intracellular region of the molecule is largely dispensable for this function. It is unlikely, therefore, that Nrg acts as a molecular 'clutch' to couple adhesion of F-actin within the growth cone to the extracellular substrate. Rather, we

  1. Differential regulation of Hes/Hey genes during inner ear development.

    PubMed

    Petrovic, Jelena; Gálvez, Hector; Neves, Joana; Abelló, Gina; Giraldez, Fernando

    2015-07-01

    Notch signaling plays a crucial role during inner ear development and regeneration. Hes/Hey genes encode for bHLH transcription factors identified as Notch targets. We have studied the expression and regulation of Hes/Hey genes during inner ear development in the chicken embryo. Among several Hes/Hey genes examined, only Hey1 and Hes5 map to the sensory regions, although with salient differences. Hey1 expression follows Jag1 expression except at early prosensory stages while Hes5 expression corresponds well to Dl1 expression throughout otic development. Although Hey1 and Hes5 are direct Notch downstream targets, they differ in the level of Notch required for activation. Moreover, they also differ in mRNA stability, showing different temporal decays after Notch blockade. In addition, Bmp, Wnt and Fgf pathways also modify Hey1 and Hes5 expression in the inner ear. Particularly, the Wnt pathway modulates Hey1 and Jag1 expression. Finally, gain of function experiments show that Hey1 and Hes5 cross-regulate each other in a complex manner. Both Hey1 and Hes5 repress Dl1 and Hes5 expression, suggesting that they prevent the transition to differentiation stages, probably by preventing Atoh1 expression. In spite of its association with Jag1, Hey1 does not seem to be instrumental for lateral induction as it does not promote Jag1 expression. We suggest that, besides being both targets of Notch, Hey1 and Hes5 are subject to a rather complex regulation that includes the stability of their transcripts, cross regulation and other signaling pathways. © 2014 Wiley Periodicals, Inc.

  2. Ear Infections and Language Development.

    ERIC Educational Resources Information Center

    Roberts, Joanne E.; Zeisel, Susan A.

    Ear infections in infants and preschoolers can cause mild or moderate temporary hearing loss, which may in turn affect a child's ability to understand and learn language. Noting that providing children with proper medical treatment for ear infections or middle ear fluid is important in preventing possible problems with language development, this…

  3. Cell-Type-Specific Modulation of Sensory Responses in Olfactory Bulb Circuits by Serotonergic Projections from the Raphe Nuclei

    PubMed Central

    Brunert, Daniela; Tsuno, Yusuke; Rothermel, Markus; Shipley, Michael T.

    2016-01-01

    Serotonergic neurons in the brainstem raphe nuclei densely innervate the olfactory bulb (OB), where they can modulate the initial representation and processing of olfactory information. Serotonergic modulation of sensory responses among defined OB cell types is poorly characterized in vivo. Here, we used cell-type-specific expression of optical reporters to visualize how raphe stimulation alters sensory responses in two classes of GABAergic neurons of the mouse OB glomerular layer, periglomerular (PG) and short axon (SA) cells, as well as mitral/tufted (MT) cells carrying OB output to piriform cortex. In PG and SA cells, brief (1–4 s) raphe stimulation elicited a large increase in the magnitude of responses linked to inhalation of ambient air, as well as modest increases in the magnitude of odorant-evoked responses. Near-identical effects were observed when the optical reporter of glutamatergic transmission iGluSnFR was expressed in PG and SA cells, suggesting enhanced excitatory input to these neurons. In contrast, in MT cells imaged from the dorsal OB, raphe stimulation elicited a strong increase in resting GCaMP fluorescence with only a slight enhancement of inhalation-linked responses to odorant. Finally, optogenetically stimulating raphe serotonergic afferents in the OB had heterogeneous effects on presumptive MT cells recorded extracellularly, with an overall modest increase in resting and odorant-evoked responses during serotonergic afferent stimulation. These results suggest that serotonergic afferents from raphe dynamically modulate olfactory processing through distinct effects on multiple OB targets, and may alter the degree to which OB output is shaped by inhibition during behavior. SIGNIFICANCE STATEMENT Modulation of the circuits that process sensory information can profoundly impact how information about the external world is represented and perceived. This study investigates how the serotonergic system modulates the initial processing of olfactory

  4. Carcinoma of the middle ear and external auditory canal

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hahn, S.S.; Kim, J.A.; Goodchild, N.

    1983-07-01

    Thirty-one patients with malignant tumors of the middle ear and external auditory canal (EAC) were observed at the University of Virginia Hospital from 1956 through 1980. Of 27 patients with carcinoma, 21 had squamous cell carcinoma, 4 had basal cell carcinoma and 2 had adenoid cystic carcinoma. The 27 patients with carcinoma are reviewed with regard to clinical presentation, treatment modality, results and complications. The majority (67%) of patients had a history of chronic ear drainage, 22% had a previous mastoidectomy or polypectomy and 7% had an associated cholesteatoma. Eighty percent of patients with carcinoma limited to EAC were alivemore » and well at 5 years, compared to 43% of patients with involvement of the middle ear. Fifty-six percent of patients without invasion of the petrous bone were alive at 5 years compared to only 20% of patients with petrous bone involvement. The data strongly suggest that survival depends on the extent of disease. The corrected disease free 5 year survival rates were 14% for patients who had surgery alone and 50% for those who had surgery and radiotherapy. Of the three patients with advanced disease who received radiotherapy alone, none survived five years.« less

  5. Hair cell regeneration in the avian auditory epithelium.

    PubMed

    Stone, Jennifer S; Cotanche, Douglas A

    2007-01-01

    Regeneration of sensory hair cells in the mature avian inner ear was first described just over 20 years ago. Since then, it has been shown that many other non-mammalian species either continually produce new hair cells or regenerate them in response to trauma. However, mammals exhibit limited hair cell regeneration, particularly in the auditory epithelium. In birds and other non-mammals, regenerated hair cells arise from adjacent non-sensory (supporting) cells. Hair cell regeneration was initially described as a proliferative response whereby supporting cells re-enter the mitotic cycle, forming daughter cells that differentiate into either hair cells or supporting cells and thereby restore cytoarchitecture and function in the sensory epithelium. However, further analyses of the avian auditory epithelium (and amphibian vestibular epithelium) revealed a second regenerative mechanism, direct transdifferentiation, during which supporting cells change their gene expression and convert into hair cells without dividing. In the chicken auditory epithelium, these two distinct mechanisms show unique spatial and temporal patterns, suggesting they are differentially regulated. Current efforts are aimed at identifying signals that maintain supporting cells in a quiescent state or direct them to undergo direct transdifferentiation or cell division. Here, we review current knowledge about supporting cell properties and discuss candidate signaling molecules for regulating supporting cell behavior, in quiescence and after damage. While significant advances have been made in understanding regeneration in non-mammals over the last 20 years, we have yet to determine why the mammalian auditory epithelium lacks the ability to regenerate hair cells spontaneously and whether it is even capable of significant regeneration under additional circumstances. The continued study of mechanisms controlling regeneration in the avian auditory epithelium may lead to strategies for inducing

  6. Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss.

    PubMed

    He, Qiang; Jia, Zhanwei; Zhang, Ying; Ren, Xiumin

    2017-03-01

    We aimed to investigate the effect of morin hydrate on neural stem cells (NSCs) isolated from mouse inner ear and its potential in protecting neuronal hearing loss. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays were employed to assess the effect of morin hydrate on the viability and proliferation of in vitro NSC culture. The NSCs were then differentiated into neurons, in which neurosphere formation and differentiation were evaluated, followed by neurite outgrowth and neural excitability measurements in the subsequent in vitro neuronal network. Mechanotransduction of cochlea ex vivo culture and auditory brainstem responses threshold and distortion product optoacoustic emissions amplitude in mouse ototoxicity model were also measured following gentamicin treatment to investigate the protective role of morin hydrate against neuronal hearing loss. Morin hydrate improved viability and proliferation, neurosphere formation and neuronal differentiation of inner ear NSCs, and promoted in vitro neuronal network functions. In both ex vivo and in vivo ototoxicity models, morin hydrate prevented gentamicin-induced neuronal hearing loss. Morin hydrate exhibited potent properties in promoting growth and differentiation of inner ear NSCs into functional neurons and protecting from gentamicin ototoxicity. Our study supports its clinical potential in treating neuronal hearing loss. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  7. Ignoring the irrelevant: auditory tolerance of audible but innocuous sounds in the bat-detecting ears of moths

    NASA Astrophysics Data System (ADS)

    Fullard, James H.; Ratcliffe, John M.; Jacobs, David S.

    2008-03-01

    Noctuid moths listen for the echolocation calls of hunting bats and respond to these predator cues with evasive flight. The African bollworm moth, Helicoverpa armigera, feeds at flowers near intensely singing cicadas, Platypleura capensis, yet does not avoid them. We determined that the moth can hear the cicada by observing that both of its auditory receptors (A1 and A2 cells) respond to the cicada’s song. The firing response of the A1 cell rapidly adapts to the song and develops spike periods in less than a second that are in excess of those reported to elicit avoidance flight to bats in earlier studies. The possibility also exists that for at least part of the day, sensory input in the form of olfaction or vision overrides the moth’s auditory responses. While auditory tolerance appears to allow H. armigera to exploit a food resource in close proximity to acoustic interference, it may render their hearing defence ineffective and make them vulnerable to predation by bats during the evening when cicadas continue to sing. Our study describes the first field observation of an eared insect ignoring audible but innocuous sounds.

  8. Pox neuro control of cell lineages that give rise to larval poly-innervated external sensory organs in Drosophila.

    PubMed

    Jiang, Yanrui; Boll, Werner; Noll, Markus

    2015-01-15

    The Pox neuro (Poxn) gene of Drosophila plays a crucial role in the development of poly-innervated external sensory (p-es) organs. However, how Poxn exerts this role has remained elusive. In this study, we have analyzed the cell lineages of all larval p-es organs, namely of the kölbchen, papilla 6, and hair 3. Surprisingly, these lineages are distinct from any previously reported cell lineages of sensory organs. Unlike the well-established lineage of mono-innervated external sensory (m-es) organs and a previously proposed model of the p-es lineage, we demonstrate that all wild-type p-es lineages exhibit the following features: the secondary precursor, pIIa, gives rise to all three support cells-socket, shaft, and sheath, whereas the other secondary precursor, pIIb, is neuronal and gives rise to all neurons. We further show that in one of the p-es lineages, that of papilla 6, one cell undergoes apoptosis. By contrast in Poxn null mutants, all p-es lineages have a reduced number of cells and their pattern of cell divisions is changed to that of an m-es organ, with the exception of a lineage in a minority of mutant kölbchen that retains a second bipolar neuron. Indeed, the role of Poxn in p-es lineages is consistent with the specification of the developmental potential of secondary precursors and the regulation of cell division but not apoptosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Shaping magnetic fields to direct therapy to ears and eyes.

    PubMed

    Shapiro, B; Kulkarni, S; Nacev, A; Sarwar, A; Preciado, D; Depireux, D A

    2014-07-11

    Magnetic fields have the potential to noninvasively direct and focus therapy to disease targets. External magnets can apply forces on drug-coated magnetic nanoparticles, or on living cells that contain particles, and can be used to manipulate them in vivo. Significant progress has been made in developing and testing safe and therapeutic magnetic constructs that can be manipulated by magnetic fields. However, we do not yet have the magnet systems that can then direct those constructs to the right places, in vivo, over human patient distances. We do not yet know where to put the external magnets, how to shape them, or when to turn them on and off to direct particles or magnetized cells-in blood, through tissue, and across barriers-to disease locations. In this article, we consider ear and eye disease targets. Ear and eye targets are too deep and complex to be targeted by a single external magnet, but they are shallow enough that a combination of magnets may be able to direct therapy to them. We focus on how magnetic fields should be shaped (in space and time) to direct magnetic constructs to ear and eye targets.

  10. Swimmer's Ear (External Otitis)

    MedlinePlus

    ... t help, your doctor might prescribe a stronger pain reliever. You'll use this only for a short time — until the ear drops and antibiotics begin to work. To protect your ear while it heals, your ...

  11. Band-like arrangement of taste-like sensory cells at the gastric groove: evidence for paracrine communication.

    PubMed

    Eberle, Julia Anna-Maria; Richter, Patric; Widmayer, Patricia; Chubanov, Vladimir; Gudermann, Thomas; Breer, Heinz

    2013-01-01

    The discovery of taste-related elements within the gastrointestinal tract has led to a growing interest in the mechanisms and physiological significance of chemosensory monitoring of chymus composition. Previous work suggests that brush cells located in the "gastric groove," which parallels the "limiting ridge," a structure in rodents that divides the fundus from the corpus, are candidate sensory cells. A novel sectioning technique revealed that these cells are arranged in a palisade-like manner forming a band which borders the whole length of the corpus epithelium. Using transgenic PLCβ2 promoter-GFP mice and specific antibodies, we have demonstrated that most of these cells express gustducin, PLCβ2, and TRPM5; typical signaling proteins of gustatory sensory "type II" cells. These molecular features strongly suggest that the cells may be capable of sensing nutrient or non-nutrient constituents of the ingested food. Since there is no evidence that brush cells are endocrine cells, attempts were made to explore how such putative chemosensory cells might transmit the information to "effector" cells. It was found that most of the cells express the neuronal nitric oxide synthase (NOS) suggesting some paracrine interaction with adjacent cells. Moreover, they also express choline acetyltransferase (ChAT) as well as the vesicular protein SNAP25, indicating the potential for cholinergic transmission, possibly with subjacent enteric nerve fibers.

  12. Band-like arrangement of taste-like sensory cells at the gastric groove: evidence for paracrine communication

    PubMed Central

    Eberle, Julia Anna-Maria; Richter, Patric; Widmayer, Patricia; Chubanov, Vladimir; Gudermann, Thomas; Breer, Heinz

    2013-01-01

    The discovery of taste-related elements within the gastrointestinal tract has led to a growing interest in the mechanisms and physiological significance of chemosensory monitoring of chymus composition. Previous work suggests that brush cells located in the “gastric groove,” which parallels the “limiting ridge,” a structure in rodents that divides the fundus from the corpus, are candidate sensory cells. A novel sectioning technique revealed that these cells are arranged in a palisade-like manner forming a band which borders the whole length of the corpus epithelium. Using transgenic PLCβ2 promoter-GFP mice and specific antibodies, we have demonstrated that most of these cells express gustducin, PLCβ2, and TRPM5; typical signaling proteins of gustatory sensory “type II” cells. These molecular features strongly suggest that the cells may be capable of sensing nutrient or non-nutrient constituents of the ingested food. Since there is no evidence that brush cells are endocrine cells, attempts were made to explore how such putative chemosensory cells might transmit the information to “effector” cells. It was found that most of the cells express the neuronal nitric oxide synthase (NOS) suggesting some paracrine interaction with adjacent cells. Moreover, they also express choline acetyltransferase (ChAT) as well as the vesicular protein SNAP25, indicating the potential for cholinergic transmission, possibly with subjacent enteric nerve fibers. PMID:23565094

  13. Influence of EARLI1-like genes on flowering time and lignin synthesis of Arabidopsis thaliana.

    PubMed

    Shi, Y; Zhang, X; Xu, Z-Y; Li, L; Zhang, C; Schläppi, M; Xu, Z-Q

    2011-09-01

    EARLI1 encodes a 14.7 kDa protein in the cell wall, is a member of the PRP (proline-rich protein) family and has multiple functions, including resistance to low temperature and fungal infection. RNA gel blot analyses in the present work indicated that expression of EARLI1-like genes, EARLI1, At4G12470 and At4G12490, was down-regulated in Col-FRI-Sf2 RNAi plants derived from transformation with Agrobacterium strain ABI, which contains a construct encoding a double-strand RNA targeting 8CM of EARLI1. Phenotype analyses revealed that Col-FRI-Sf2 RNAi plants of EARLI1 flowered earlier than Col-FRI-Sf2 wild-type plants. The average bolting time of Col-FRI-Sf2 and Col-FRI-Sf2 RNAi plants was 39.7 and 19.4 days, respectively, under a long-day photoperiod. In addition, there were significant differences in main stem length, internode number and rosette leaf number between Col-FRI-Sf2 and Col-FRI-Sf2 RNAi plants. RT-PCR showed that EARLI1-like genes might delay flowering time through the autonomous and long-day photoperiod pathways by maintaining the abundance of FLC transcripts. In Col-FRI-Sf2 RNAi plants, transcription of FLC was repressed, while expression of SOC1 and FT was activated. Microscopy observations showed that EARLI1-like genes were also associated with morphogenesis of leaf cells in Arabidopsis. Using histochemical staining, EARLI1-like genes were found to be involved in regulation of lignin synthesis in inflorescence stems, and Col-FRI-Sf2 and Col-FRI-Sf2 RNAi plants had 9.67% and 8.76% dry weight lignin, respectively. Expression analysis revealed that cinnamoyl-CoA reductase, a key enzyme in lignin synthesis, was influenced by EARLI1-like genes. These data all suggest that EARLI1-like genes could control the flowering process and lignin synthesis in Arabidopsis. © 2011 German Botanical Society and The Royal Botanical Society of the Netherlands.

  14. Ear molding in newborn infants with auricular deformities.

    PubMed

    Byrd, H Steve; Langevin, Claude-Jean; Ghidoni, Lorraine A

    2010-10-01

    A review of a single physician's experience in managing over 831 infant ear deformities (488 patients) is presented. The authors' methods of molding have advanced from the use of various tapes, glues, and stents, to a comprehensive yet simple system that shapes the antihelix, the triangular fossa, the helical rim, and the overly prominent conchal-mastoid angle (EarWell Infant Ear Correction System). The types of deformities managed, and their relative occurrence, are as follows: (1) prominent/cup ear, 373 ears (45 percent); (2) lidding/lop ear, 224 ears (27 percent); (3) mixed ear deformities, 83 ears (10 percent) (all had associated conchal crus); (4) Stahl's ear, 66 ears (8 percent); (5) helical rim abnormalities, 58 ears (7 percent); (6) conchal crus, 25 ears (3 percent); and (7) cryptotia, two ears (0.2 percent). Bilateral deformities were present in 340 patients (70 percent), with unilateral deformities in 148 patients (30 percent). Fifty-eight infant ears (34 patients) were treated using the final version of the EarWell Infant Ear Correction System with a success rate exceeding 90 percent (good to excellent results). The system was found to be most successful when begun in the first week of the infant's life. When molding was initiated after 3 weeks from birth, only approximately half of the infants had a good response. Congenital ear deformities are common and only approximately 30 percent self-correct. These deformities can be corrected by initiating appropriate molding in the first week of life. Neonatal molding reduces the need for surgical correction with results that often exceed what can be achieved with the surgical alternative.

  15. Characteristics of laser-induced shock wave injury to the inner ear of rats

    NASA Astrophysics Data System (ADS)

    Kurioka, Takaomi; Matsunobu, Takeshi; Niwa, Katsuki; Tamura, Atsushi; Kawauchi, Satoko; Satoh, Yasushi; Sato, Shunichi; Shiotani, Akihiro

    2014-12-01

    Recently, the number of blast injuries of the inner ear has increased in the general population. In blast-induced inner ear injury, a shock wave (SW) component in the blast wave is considered to play an important role in sensorineural hearing loss. However, the mechanisms by which an SW affects inner ear tissue remain largely unknown. We aimed to establish a new animal model for SW-induced inner ear injury by using laser-induced SWs (LISWs) on rats. The LISWs were generated by irradiating an elastic laser target with 694-nm nanosecond pulses of a ruby laser. After LISW application to the cochlea through bone conduction, auditory measurements revealed the presence of inner ear dysfunction, the extent of which depended on LISW overpressure. A significantly lower survival rate of hair cells and spiral ganglion neurons, as well as severe oxidative damage, were observed in the inner ear exposed to an LISW. Although considerable differences in the pressure characteristics exist between LISWs and SWs in real blast waves, the functional and morphological changes shown by the present LISW-based model were similar to those observed in real blast-induced injury. Thus, our animal model is expected to be useful for laboratory-based research of blast-induced inner ear injury.

  16. Characteristics of laser-induced shock wave injury to the inner ear of rats.

    PubMed

    Kurioka, Takaomi; Matsunobu, Takeshi; Niwa, Katsuki; Tamura, Atsushi; Kawauchi, Satoko; Satoh, Yasushi; Sato, Shunichi; Shiotani, Akihiro

    2014-12-01

    Recently, the number of blast injuries of the inner ear has increased in the general population. In blast-induced inner ear injury, a shock wave (SW) component in the blast wave is considered to play an important role in sensorineural hearing loss. However, the mechanisms by which an SW affects inner ear tissue remain largely unknown. We aimed to establish a new animal model for SW-induced inner ear injury by using laser-induced SWs (LISWs) on rats. The LISWs were generated by irradiating an elastic laser target with 694-nm nanosecond pulses of a ruby laser. After LISW application to the cochlea through bone conduction, auditory measurements revealed the presence of inner ear dysfunction, the extent of which depended on LISW overpressure. A significantly lower survival rate of hair cells and spiral ganglion neurons, as well as severe oxidative damage, were observed in the inner ear exposed to an LISW. Although considerable differences in the pressure characteristics exist between LISWs and SWs in real blast waves, the functional and morphological changes shown by the present LISW-based model were similar to those observed in real blast-induced injury. Thus, our animal model is expected to be useful for laboratory-based research of blast-induced inner ear injury.

  17. Ewing Sarcoma of the External Ear Canal

    PubMed Central

    Kecelioglu Binnetoglu, Kiymet; Gerin, Fatma; Sari, Murat

    2016-01-01

    Background. Ewing sarcoma (ES) is a high-grade malignant tumor that has skeletal and extraskeletal forms and consists of small round cells. In the head and neck region, reported localization of extraskeletal ES includes the larynx, thyroid gland, submandibular gland, nasal fossa, pharynx, skin, and parotid gland, but not the external ear canal. Methods. We present the unique case of a 2-year-old boy with extraskeletal ES arising from the external ear canal, mimicking auricular hematoma. Results. Surgery was performed and a VAC/IE (vincristine, adriamycin, cyclophosphamide alternating with ifosfamide, and etoposide) regimen was used for adjuvant chemotherapy for 12 months. Conclusion. The clinician should consider extraskeletal ES when diagnosing tumors localized in the head and neck region because it may be manifested by a nonspecific clinical picture mimicking common otorhinolaryngologic disorders. PMID:27313930

  18. Neural stem/progenitor cell properties of glial cells in the adult mouse auditory nerve

    PubMed Central

    Lang, Hainan; Xing, Yazhi; Brown, LaShardai N.; Samuvel, Devadoss J.; Panganiban, Clarisse H.; Havens, Luke T.; Balasubramanian, Sundaravadivel; Wegner, Michael; Krug, Edward L.; Barth, Jeremy L.

    2015-01-01

    The auditory nerve is the primary conveyor of hearing information from sensory hair cells to the brain. It has been believed that loss of the auditory nerve is irreversible in the adult mammalian ear, resulting in sensorineural hearing loss. We examined the regenerative potential of the auditory nerve in a mouse model of auditory neuropathy. Following neuronal degeneration, quiescent glial cells converted to an activated state showing a decrease in nuclear chromatin condensation, altered histone deacetylase expression and up-regulation of numerous genes associated with neurogenesis or development. Neurosphere formation assays showed that adult auditory nerves contain neural stem/progenitor cells (NSPs) that were within a Sox2-positive glial population. Production of neurospheres from auditory nerve cells was stimulated by acute neuronal injury and hypoxic conditioning. These results demonstrate that a subset of glial cells in the adult auditory nerve exhibit several characteristics of NSPs and are therefore potential targets for promoting auditory nerve regeneration. PMID:26307538

  19. Changes in immunostaining of inner ears after antigen challenge into the scala tympani.

    PubMed

    Ichimiya, I; Kurono, Y; Hirano, T; Mogi, G

    1998-04-01

    To study the mechanisms of immune responses and immune injuries in inner ears, labyrinthitis was induced by inoculation of keyhole limpet hemocyanin (KLH) into the scala tympani of systemically sensitized guinea pigs. Inner ears were then immunostained for KLH, immunoglobulin G (IgG), albumin, connexin26 (Cx26), and sodium-potassium adenosine triphosphate (Na,K-ATPase). Inflammatory cells containing KLH were observed in the scala tympani and in the collecting venule of the spiral modiolar vein (SMV). Spiral ligament, spiral limbus, and blood vessels including the SMV were diffusely positive for IgG and albumin. Immunoreactivity for Cx26 and Na,K-ATPase was decreased compared with the normal ears in the fibrocytes of the spiral ligament. These results suggest that inflammatory cells and blood constituents could extravasate into the cochlea from blood vessels and that fibrocyte damage in the spiral ligament could cause cochlear dysfunction.

  20. [The effect of OSAHS on middle ear and inner ear vestibule function advances].

    PubMed

    Li, K L; Li, J R

    2016-05-20

    Obstructive sleep apnea hypopnea syndrome(OSAHS) as a common frequentlyoccurring disease, it can cause repeated episodes of hypoxaemia and hypercapnia during sleep. With long period of hypoxaemia, obvious pathological changes and dysfunction emerged in heart,brain and lung then all kinds of clinical symptoms appear. Because of the middle ear and inner ear themselves anatomical characteristics and blood supply of regulating mechanism, they often has been damaged before the other important organ damage. As scholars have indepth study of the auditory system complications in patients with OSAHS, various influence of OSAHS on the middle ear,inner ear also gradually be known.This paper will review the effect of OSAHS on middle ear, inner ear and vestibule function, hope to have some application value for clinical work. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

  1. Listening to the ear

    NASA Astrophysics Data System (ADS)

    Shera, Christopher A.

    Otoacoustic emissions demonstrate that the ear creates sound while listening to sound, offering a promising acoustic window on the mechanics of hearing in awake, listening human beings. That window is clouded, however, by an incomplete knowledge of wave reflection and transmission, both forth and back within the cochlea and through the middle ear. This thesis "does windows," addressing wave propagation and scattering on both sides of the middle ear. A summary of highlights follows. Measurements of the cochlear input impedance in cat are used to identify a new symmetry in cochlear mechanics-termed "tapering symmetry" after its geometric interpretation in simple models-that guarantees that the wavelength of the traveling wave changes slowly with position near the stapes. Waves therefore propagate without reflection through the basal turns of the cochlea. Analytic methods for solving the cochlear wave equations using a perturbative scattering series are given and used to demonstrate that, contrary to common belief, conventional cochlear models exhibit negligible internal reflection whether or not they accurately represent the tapering symmetries of the inner ear. Frameworks for the systematic "deconstruction" of eardrum and middle-ear transduction characteristics are developed and applied to the analysis of noninvasive measurements of middle-ear and cochlear mechanics. A simple phenomenological model of inner-ear compressibility that correctly predicts hearing thresholds in patients with missing or disarticulated middle-ear ossicles is developed and used to establish an upper bound on cochlear compressibility several orders of magnitude smaller than that provided by direct measurements. Accurate measurements of stimulus frequency evoked otoacoustic emissions are performed and used to determine the form and frequency variation of the cochlear traveling-wave ratio noninvasively. Those measurements are inverted to obtain the spatial distribution of mechanical

  2. Listening to the Ear

    NASA Astrophysics Data System (ADS)

    Shera, Christopher Alan

    Otoacoustic emissions demonstrate that the ear creates sound while listening to sound, offering a promising acoustic window on the mechanics of hearing in awake, listening human beings. That window is clouded, however, by an incomplete knowledge of wave reflection and transmission, both forth and back within the cochlea and through the middle ear. This thesis "does windows," addressing wave propagation and scattering on both sides of the middle ear. A summary of highlights follows. Measurements of the cochlear input impedance in cat are used to identify a new symmetry in cochlear mechanics--termed "tapering symmetry" after its geometric interpretation in simple models--that guarantees that the wavelength of the traveling wave changes slowly with position near the stapes. Waves therefore propagate without reflection through the basal turns of the cochlea. Analytic methods for solving the cochlear wave equations using a perturbative scattering series are given and used to demonstrate that, contrary to common belief, conventional cochlear models exhibit negligible internal reflection whether or not they accurately represent the tapering symmetries of the inner ear. Frameworks for the systematic "deconstruction" of eardrum and middle-ear transduction characteristics are developed and applied to the analysis of noninvasive measurements of middle-ear and cochlear mechanics. A simple phenomenological model of inner-ear compressibility that correctly predicts hearing thresholds in patients with missing or disarticulated middle-ear ossicles is developed and used to establish an upper bound on cochlear compressibility several orders of magnitude smaller than that provided by direct measurements. Accurate measurements of stimulus -frequency evoked otoacoustic emissions are performed and used to determine the form and frequency variation of the cochlear traveling-wave ratio noninvasively. Those measurements are inverted to obtain the spatial distribution of mechanical

  3. Ear fibroblasts derived from Taiwan yellow cattle are more heat resistant than those from Holstein cattle.

    PubMed

    Wu, Hung-Yi; Peng, Shao-Yu; Li, Hung; Lee, Jai-Wei; Kesorn, Piyawit; Wu, Hsi-Hsun; Ju, Jyh-Cherng; Shen, Perng-Chih

    2017-05-01

    The objective of this study was to compare the thermotolerances of ear fibroblasts derived from Holstein (H) and Taiwan yellow cattle (Y) and their apoptosis-related protein expressions with (1, 3, 6, 12, and 24h) or without heat shock treatment. The results showed that the vaginal temperatures of Y (38.4-38.5°C) were (P<0.05) lower than that of H (38.8°C) during the hot season. The apoptotic rates of ear fibroblasts derived from Y (6h: 1.1%; 12h: 1.6%; 24h: 2.6%) were lower (P<0.05) than those of cells derived from H (6h: 1.8%; 12h: 4.0%; 24h: 6.9%), respectively, after heat shock (42°C). The expression level of apoptosis inducing factor (AIF) in ear fibroblasts derived from H was higher (P<0.05) than those derived from Y after the heat shock treatment for 6h and 12h, respectively. The level of cytochrome c of ear fibroblasts derived from H was higher (P<0.05) than those derived from Y after the heat shock treatment for 1-12h, respectively. The abundances of Caspase-3, Caspase-8 and Caspase-9 of ear fibroblasts derived from H were higher (P<0.05) than those of cells derived from Y after 12h and 24h of heat shock, respectively; the Bcl-2/Bax ratios of ear fibroblasts derived from H were lower (P<0.05) than those from Y-derived fibroblasts after heated for 1-24h. The expression level of HSP-70 of Y-derived ear fibroblasts was also higher (P<0.05) than that from H after the same duration of heat shock treatments. Taken together, the thermotolerance of ear fibroblasts derived from Taiwan yellow cattle was better than that of cells derived from Holstein cattle. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Modulatory role of sensory innervation on hair follicle stem cell progeny during wound healing of the rat skin.

    PubMed

    Martínez-Martínez, Eduardo; Galván-Hernández, Claudio I; Toscano-Márquez, Brenda; Gutiérrez-Ospina, Gabriel

    2012-01-01

    The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing. We used neonatal capsaicin treatment to reduce sensory terminals in the rat skin and performed morphometric analyses using design-based stereological methods. Epithelial proliferation was analyzed by quantifying the number of bromodeoxyuridine-labeled (BrdU(+)) nuclei in the epidermis and hair follicles. After wounding, the epidermis of capsaicin-treated rats presented fewer BrdU(+) nuclei than in control rats. To assess SC progeny migration, we employed a double labeling protocol with iododeoxyuridine and chlorodeoxyuridine (IdU(+)/CldU(+)). The proportion of double-labeled cells was similar in the hair follicles of both groups at 32 h postwounding. IdU(+)/CldU(+) cell proportion increased in the epidermis of control rats and decreased in treated rats at 61 h postwounding. The epidermal volume immunostained for keratin 6 was greater in treated rats at 61 h. Confocal microscopy analysis revealed that substance P (SP) and calcitonin gene-related peptide (CGRP) receptor immunoreactivity were both present in CD34(+) and BrdU-retaining cells of the hair follicles. Our results suggest that capsaicin denervation impairs SC progeny egress from the hair follicles, a circumstance associated with a greater epidermal activation. Altogether, these phenomena would explain the longer times for healing in denervated skin. Thus, sensory innervation may play a functional role in the modulation of hair

  5. Hair cell heterogeneity and ultrasonic hearing: recent advances in understanding fish hearing.

    PubMed Central

    Popper, A N

    2000-01-01

    The past decade has seen a wealth of new data on the auditory capabilities and mechanisms of fishes. We now have a significantly better appreciation of the structure and function of the auditory system in fishes with regard to their peripheral and central anatomy, physiology, behaviour, sound source localization and hearing capabilities. This paper deals with two of the newest of these findings, hair cell heterogeneity and the detection of ultrasound. As a result of this recent work, we now know that fishes have several different types of sensory hair cells in both the ear and lateral line and there is a growing body of evidence to suggest that these hair cell types arose very early in the evolution of the octavolateralis system. There is also some evidence to suggest that the differences in the hair cell types have functional implications for the way the ear and lateral line of fishes detect and process stimuli. Behavioural studies have shown that, whereas most fishes can only detect sound to 1-3 kHz, several species of the genus Alosa (Clupeiformes, i.e. herrings and their relatives) can detect sounds up to 180 kHz (or even higher). It is suggested that this capability evolved so that these fishes can detect one of their major predators, echolocating dolphins. The mechanism for ultrasound detection remains obscure, though it is hypothesized that the highly derived utricle of the inner ear in these species is involved. PMID:11079414

  6. Effect of Hypergravity on Carbonanhydrase Reactivity in inner Ear Ioncytes of developing Cichlid Fish

    NASA Astrophysics Data System (ADS)

    Beier, M.; Anken, R.; Rahmann, H.

    It has been shown earlier that hypergravity slows down inner ear otolith growth in developing fish. Otolith growth in terms of mineralisation mainly depends on the enzyme carboanhydrase (CAH), which is responsible for the provision of the pH- value necessary for calcium carbonate deposition and thus also is presumed to play a prominent role in Ménière's disease (a sensory - motor disorder inducing vertigo and kinetosis). Larval siblings of cichlid fish (Oreochromis mossambicus) were subjected to hypergravity (3g; 6 hours) during development and separated into normally and kinetotically swimming individuals following the transfer to 1g (i.e., stopping the centrifuge; kinetotically behaving fish performed spinning movements). Subsequently, CAH was histochemically demonstrated in inner ear ionocytes (cells involved in the endolymphatic ion exchange) and enzyme reactivity was determined densitometrically. The results showed that CAH-reactivity was significantly increased in normally behaving hyper-g specimens as compared to controls kept at 1g, whereas no difference in enzyme reactivity was evident between the controls and kinetotically behaving fish. On the background of earlier studies, according to which (1) hypergravity induces a decrease of otolith growth and (2) the otolithic calcium incorporation (visualized using the calcium -tracer alizarin complexone) of kinetotically swimming hyper - g fish was lower as compared to normally behaving hyper - g animals, the present study strongly supports the concept that an increase in CAH-reactivity may result in a decrease of otolithic calcium deposition. The mechanism regulating CAH-activity hitherto remains to be determined. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 9997).

  7. A morphometric study of the human ear.

    PubMed

    Alexander, K Skaria; Stott, David J; Sivakumar, Branavan; Kang, Norbert

    2011-01-01

    We examined variations in the shape of the human ear according to age, sex and ethnic group with particular attention to ear prominence. 420 volunteers were recruited. Measurements included; head height and length, ear height and axis, antihelix taken off angle, earlobe length and width, ear width at the helical root and tragus. Prominence was measured at the helical root and tragus (conchomastoid angle, conchal bowl depth and helical-mastoid distance). Good symmetry was shown for all measurements. Ethnically Indian volunteers had the largest ears (both length and width), followed by Caucasians, and Afro-Caribbeans. This trend was significant in males (p<0.001), but not significant in females (p=0.087). Ears increased in size throughout life. Subjectively, only 2% of volunteers felt their ears were prominent compared to 10% in the opinion of the principal investigator. No objective measurements were identified that accurately predicted subjective perceptions of prominence. We found consistent trends in ear morphology depending on ethnic group, age and sex. Our study was unable to define an objective method for assessing ear prominence. Decisions about what constitutes a prominent ear should be left to personal and aesthetic choice. Copyright © 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  8. Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c.

    PubMed

    Pan, Bifeng; Askew, Charles; Galvin, Alice; Heman-Ackah, Selena; Asai, Yukako; Indzhykulian, Artur A; Jodelka, Francine M; Hastings, Michelle L; Lentz, Jennifer J; Vandenberghe, Luk H; Holt, Jeffrey R; Géléoc, Gwenaëlle S

    2017-03-01

    Because there are currently no biological treatments for hearing loss, we sought to advance gene therapy approaches to treat genetic deafness. We focused on Usher syndrome, a devastating genetic disorder that causes blindness, balance disorders and profound deafness, and studied a knock-in mouse model, Ush1c c.216G>A, for Usher syndrome type IC (USH1C). As restoration of complex auditory and balance function is likely to require gene delivery systems that target auditory and vestibular sensory cells with high efficiency, we delivered wild-type Ush1c into the inner ear of Ush1c c.216G>A mice using a synthetic adeno-associated viral vector, Anc80L65, shown to transduce 80-90% of sensory hair cells. We demonstrate recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders.

  9. Development and regeneration of vestibular hair cells in mammals.

    PubMed

    Burns, Joseph C; Stone, Jennifer S

    2017-05-01

    Vestibular sensation is essential for gaze stabilization, balance, and perception of gravity. The vestibular receptors in mammals, Type I and Type II hair cells, are located in five small organs in the inner ear. Damage to hair cells and their innervating neurons can cause crippling symptoms such as vertigo, visual field oscillation, and imbalance. In adult rodents, some Type II hair cells are regenerated and become re-innervated after damage, presenting opportunities for restoring vestibular function after hair cell damage. This article reviews features of vestibular sensory cells in mammals, including their basic properties, how they develop, and how they are replaced after damage. We discuss molecules that control vestibular hair cell regeneration and highlight areas in which our understanding of development and regeneration needs to be deepened. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Synaptic plasticity and sensory-motor improvement following fibrin sealant dorsal root reimplantation and mononuclear cell therapy

    PubMed Central

    Benitez, Suzana U.; Barbizan, Roberta; Spejo, Aline B.; Ferreira, Rui S.; Barraviera, Benedito; Góes, Alfredo M.; de Oliveira, Alexandre L. R.

    2014-01-01

    Root lesions may affect both dorsal and ventral roots. However, due to the possibility of generating further inflammation and neuropathic pain, surgical procedures do not prioritize the repair of the afferent component. The loss of such sensorial input directly disturbs the spinal circuits thus affecting the functionality of the injuried limb. The present study evaluated the motor and sensory improvement following dorsal root reimplantation with fibrin sealant (FS) plus bone marrow mononuclear cells (MC) after dorsal rhizotomy. MC were used to enhance the repair process. We also analyzed changes in the glial response and synaptic circuits within the spinal cord. Female Lewis rats (6–8 weeks old) were divided in three groups: rhizotomy (RZ group), rhizotomy repaired with FS (RZ+FS group) and rhizotomy repaired with FS and MC (RZ+FS+MC group). The behavioral tests electronic von-Frey and Walking track test were carried out. For immunohistochemistry we used markers to detect different synapse profiles as well as glial reaction. The behavioral results showed a significant decrease in sensory and motor function after lesion. The reimplantation decreased glial reaction and improved synaptic plasticity of afferent inputs. Cell therapy further enhanced the rewiring process. In addition, both reimplanted groups presented twice as much motor control compared to the non-treated group. In conclusion, the reimplantation with FS and MC is efficient and may be considered an approach to improve sensory-motor recovery following dorsal rhizotomy. PMID:25249946

  11. Signatures from Tissue-specific MPSS Libraries Identify Transcripts Preferentially Expressed in the Mouse Inner Ear

    PubMed Central

    Peters, Linda M.; Belyantseva, Inna A.; Lagziel, Ayala; Battey, James F.; Friedman, Thomas B.; Morell, Robert J.

    2007-01-01

    Specialization in cell function and morphology is influenced by the differential expression of mRNAs, many of which are expressed at low abundance and restricted to certain cell types. Detecting such transcripts in cDNA libraries may require sequencing millions of clones. Massively parallel signature sequencing (MPSS) is well-suited for identifying transcripts that are expressed in discrete cell types and in low abundance. We have made MPSS libraries from microdissections of three inner ear tissues. By comparing these MPSS libraries to those of 87 other tissues included in the Mouse Reference Transcriptome (MRT) online resource, we have identified genes that are highly enriched in, or specific to, the inner ear. We show by RT-PCR and in situ hybridization that signatures unique to the inner ear libraries identify transcripts with highly specific cell-type localizations. These transcripts serve to illustrate the utility of a resource that is available to the research community. Utilization of these resources will increase the number of known transcription units and expand our knowledge of the tissue-specific regulation of the transcriptome. PMID:17049805

  12. Listening to Nature's orchestra with peculiar ears

    NASA Astrophysics Data System (ADS)

    Yager, David D.

    2003-04-01

    Insects use hearing for the crucial tasks of communicating with conspecifics and avoiding predators. Although all are based on the same acoustic principles, the diversity of insect ears is staggering and instructive. For instance, a South African grasshopper demonstrates that hearing conspecific calls is possible over distances 1 km with ears that do not have tympana. Actually, these creatures have six pairs of ears that play different roles in behavior. In numerical contrast, praying mantises have just a single ear in the ventral midline. The ear is very effective at detecting ultrasonic bat cries. However, the bioacoustics of sound transduction by two tympana facing each other in a deep, narrow slit is a puzzle. Tachinid flies demonstrate that directional hearing at 5 kHz is possible with a pair of ears fused together to give a total size of 1 mm. The ears are under the fly's chin. Hawk moths have their ears built into their mouthparts and the tympanum is more like a hollow ball than the usual membrane. As an apt last example, cicada ears are actually part of the orchestra: their tympana function both in sound reception and sound production.

  13. Unclassified congenital deformities of the external ear.

    PubMed

    Vathulya, Madhubari

    2018-01-01

    Congenital ear deformities are a common entity. They are found in isolation or as a part of syndrome in patients. They may involve the external, middle or inner ear or in any of these combinations. Three patients of different ages presented with deformities including mirror image duplication of the superior auricle, unclassified deformities of ear lobule (wavy lobule) and deformity of superior auricle with unclassified variety of lateral ear pit. This article highlights that there are further cases of ear deformities that are noticed in the general population who come for cosmetic correction, and hence, there is a need for further modifying the classification of ear deformities.

  14. Ultrasound characterization of middle ear effusion.

    PubMed

    Seth, Rahul; Discolo, Christopher M; Palczewska, Grazyna M; Lewandowski, Jan J; Krakovitz, Paul R

    2013-01-01

    To further enhance and assess the ability to characterize middle ear effusion (MEE) using non-invasive ultrasound technology. This is a prospective unblinded comparison study. Fifty-six children between the ages of 6 months and 17 years scheduled to undergo bilateral myringotomy with pressure equalization tube placement were enrolled. With the child anesthetized, the probe was placed into the external ear canal after sterile water was inserted. Ultrasound recordings of middle ear contents were analyzed by computer algorithm. Middle ear fluid was collected during myringotomy and analyzed for bacterial culture and viscosity. Ultrasound waveforms yielded a computer algorithm interpretation of middle ear contents in 66% of ears tested. When a result was obtained, the sensitivity and specificity for successfully characterizing middle ear fluid content as either void of fluid, thick fluid (mucoid), or thin fluid (serous or purulent) were at least 94%. Mucoid effusions had higher measured viscosity values (P=.002). Viscosity measures were compared to culture result, and those with low viscosity (thin consistency) had a higher likelihood of having a positive culture (P=.048). The device sensitivity and specificity for fluid detection were 94% or greater among interpretable waveforms (66% of those tested). Although this technology provides important information of the middle ear effusion presence and characteristic, further technological improvements are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Ultrasound Characterization of Middle Ear Effusion

    PubMed Central

    Seth, Rahul; Discolo, Christopher M; Palczewska, Grazyna M; Lewandowski, Jan J; Krakovitz, Paul R

    2012-01-01

    Purpose To further enhance and assess the ability to characterize middle ear effusion (MEE) using non-invasive ultrasound technology. Materials and Methods This is a prospective unblinded comparison study. Fifty-six children between the ages of 6 months and 17 years scheduled to undergo bilateral myringotomy with pressure equalization tube placement were enrolled. With the child anesthetized, the probe was placed into the external ear canal after sterile water was inserted. Ultrasound recordings of middle ear contents were analyzed by computer algorithm. Middle ear fluid was collected during myringotomy and analyzed for bacterial culture and viscosity. Results Ultrasound waveforms yielded a computer algorithm interpretation of middle ear contents in 66% of ears tested. When a result was obtained, the sensitivity and specificity for successfully characterizing middle ear fluid content as either void of fluid, thick fluid (mucoid), or thin fluid (serous or purulent) was at least 94%. Mucoid effusions had higher measured viscosity values (P=0.002). Viscosity measures were compared to culture result, and those with low viscosity (thin consistency) had a higher likelihood of having a positive culture (P=0.048). Conclusion The device sensitivity and specificity for fluid detection was 94% or greater among interpretable waveforms (66% of those tested). Although this technology provides important information of the middle ear effusion presence and characteristic, further technological improvements are needed. PMID:23084430

  16. Integrin α8 and Pcdh15 act as a complex to regulate cilia biogenesis in sensory cells.

    PubMed

    Goodman, Linda; Zallocchi, Marisa

    2017-11-01

    The way an organism perceives its surroundings depends on sensory systems and the highly specialized cilia present in the neurosensory cells. Here, we describe the existence of an integrin α8 (Itga8) and protocadherin-15a (Pcdh15a) ciliary complex in neuromast hair cells in a zebrafish model. Depletion of the complex via downregulation or loss-of-function mutation leads to a dysregulation of cilia biogenesis and endocytosis. At the molecular level, removal of the complex blocks the access of Rab8a into the cilia as well as normal recruitment of ciliary cargo by centriolar satellites. These defects can be reversed by the introduction of a constitutively active form of Rhoa, suggesting that Itga8-Pcdh15a complex mediates its effect through the activation of this small GTPase and probably by the regulation of actin cytoskeleton dynamics. Our data points to a novel mechanism involved in the regulation of sensory cilia development, with the corresponding implications for normal sensory function. © 2017. Published by The Company of Biologists Ltd.

  17. Age-Related Sensory Impairments and Risk of Cognitive Impairment

    PubMed Central

    Fischer, Mary E; Cruickshanks, Karen J.; Schubert, Carla R; Pinto, Alex A; Carlsson, Cynthia M; Klein, Barbara EK; Klein, Ronald; Tweed, Ted S.

    2016-01-01

    Background/Objectives To evaluate the associations of sensory impairments with the 10-year risk of cognitive impairment. Previous work has primarily focused on the relationship between a single sensory system and cognition. Design The Epidemiology of Hearing Loss Study (EHLS) is a longitudinal, population-based study of aging in the Beaver Dam, WI community. Baseline examinations were conducted in 1993 and follow-up exams have been conducted every 5 years. Setting General community Participants EHLS members without cognitive impairment at EHLS-2 (1998–2000). There were 1,884 participants (mean age = 66.7 years) with complete EHLS-2 sensory data and follow-up information. Measurements Cognitive impairment was a Mini-Mental State Examination score of < 24 or history of dementia or Alzheimer’s disease. Hearing impairment was a pure-tone average of hearing thresholds (0.5, 1, 2 and 4 kHz) of > 25 decibel Hearing Level in either ear. Visual impairment was Pelli-Robson contrast sensitivity of < 1.55 log units in the better eye and olfactory impairment was a San Diego Odor Identification Test score of < 6. Results Hearing, visual, and olfactory impairment were independently associated with cognitive impairment risk [Hearing: Hazard Ratio (HR) = 1.90, 95% Confidence Interval (C.I.) = 1.11, 3.26; Vision: HR = 2.05, 95% C.I. = 1.24, 3.38; Olfaction: HR = 3.92, 95% C.I. = 2.45, 6.26]. However, 85% with hearing impairment, 81% with visual impairment, and 76% with olfactory impairment did not develop cognitive impairment during follow-up. Conclusion The relationship between sensory impairment and cognitive impairment was not unique to one sensory system suggesting sensorineural health may be a marker of brain aging. The development of a combined sensorineurocognitive measure may be useful in uncovering mechanisms of healthy brain aging. PMID:27611845

  18. Is Attention Shared Between the Ears?1

    PubMed Central

    Shiffrin, Richard M.; Pisoni, David B.; Castaneda-Mendez, Kicab

    2012-01-01

    This study tests the locus of attention during selective listening for speech-like stimuli. Can processing be differentially allocated to the two ears? Two conditions were used. The simultaneous condition involved one of four randomly chosen stop-consonants being presented to one of the ears chosen at random. The sequential condition involved two intervals; in the first S listened to the right ear; in the second S listened to the left ear. One of the four consonants was presented to an attended ear during one of these intervals. Experiment I used no distracting stimuli. Experiment II utilized a distracting consonant not confusable with any of the four target consonants. This distractor was always presented to any ear not containing a target. In both experiments, simultaneous and sequential performance were essentially identical, despite the need for attention sharing between the two ears during the simultaneous condition. We conclude that selective attention does not occur during perceptual processing of speech sounds presented to the two ears. We suggest that attentive effects arise in short-term memory following processing. PMID:23226838

  19. 21 CFR 870.2710 - Ear oximeter.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ear oximeter. 870.2710 Section 870.2710 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices § 870.2710 Ear oximeter. (a) Identification. An ear...

  20. Can Loud Music Hurt My Ears?

    MedlinePlus

    ... Videos for Educators Search English Español Can Loud Music Hurt My Ears? KidsHealth / For Kids / Can Loud Music Hurt My Ears? Print en español La música ... up? Oh! You want to know if loud music can hurt your ears . Are you asking because ...

  1. 21 CFR 870.2710 - Ear oximeter.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ear oximeter. 870.2710 Section 870.2710 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices § 870.2710 Ear oximeter. (a) Identification. An ear...

  2. Mammalian Otolin: A Multimeric Glycoprotein Specific to the Inner Ear that Interacts with Otoconial Matrix Protein Otoconin-90 and Cerebellin-1

    PubMed Central

    Deans, Michael R.; Peterson, Jonathan M.; Wong, G. William

    2010-01-01

    Background The mammalian otoconial membrane is a dense extracellular matrix containing bio-mineralized otoconia. This structure provides the mechanical stimulus necessary for hair cells of the vestibular maculae to respond to linear accelerations and gravity. In teleosts, Otolin is required for the proper anchoring of otolith crystals to the sensory maculae. Otoconia detachment and subsequent entrapment in the semicircular canals can result in benign paroxysmal positional vertigo (BPPV), a common form of vertigo for which the molecular basis is unknown. Several cDNAs encoding protein components of the mammalian otoconia and otoconial membrane have recently been identified, and mutations in these genes result in abnormal otoconia formation and balance deficits. Principal Findings Here we describe the cloning and characterization of mammalian Otolin, a protein constituent of otoconia and the otoconial membrane. Otolin is a secreted glycoprotein of ∼70 kDa, with a C-terminal globular domain that is homologous to the immune complement C1q, and contains extensive posttranslational modifications including hydroxylated prolines and glycosylated lysines. Like all C1q/TNF family members, Otolin multimerizes into higher order oligomeric complexes. The expression of otolin mRNA is restricted to the inner ear, and immunohistochemical analysis identified Otolin protein in support cells of the vestibular maculae and semi-circular canal cristae. Additionally, Otolin forms protein complexes with Cerebellin-1 and Otoconin-90, two protein constituents of the otoconia, when expressed in vitro. Otolin was also found in subsets of support cells and non-sensory cells of the cochlea, suggesting that Otolin is also a component of the tectorial membrane. Conclusion Given the importance of Otolin in lower organisms, the molecular cloning and biochemical characterization of the mammalian Otolin protein may lead to a better understanding of otoconial development and vestibular dysfunction

  3. Association Between Sensory Impairment and Dementia in Older Adults: Evidence from China.

    PubMed

    Luo, Yanan; He, Ping; Guo, Chao; Chen, Gong; Li, Ning; Zheng, Xiaoying

    2018-03-01

    To determine the association between sensory impairment and dementia in Chinese older adults. Cross-sectional. Older adults in 31 provinces of China. Individuals aged 65 and older (N = 250,752). Psychiatrists ascertained dementia based on the International Classification of Diseases, 10th Revision. Sensory impairment was measured as only hearing impairment, only vision impairment, and combined sensory impairment (combined hearing and vision impairment). Hearing impairment was defined as greater than 40 dB loss in the better ear according to the standard of the World Health Organization (WHO) Prevention of Deafness and Hearing Impairment (PDH) standard 97.3. Ophthalmologists assessed vision impairment according to the WHO best-corrected visual acuity (BCVA) criteria (low vision: 0.05≤BCVA ≤0.29; blindness: no light perception ≤ BCVA <0.05, visual field less than 10 degrees; the better-seeing eye). The prevalence of dementia was 0.41% (95% CI = 0.39-0.44%) without sensory impairment, 0.83% (95% CI = 0.70-0.99%) with only visual impairment, 0.61 (95% CI = 0.53-0.71%) with only hearing impairment, and 1.27% (95% CI = 1.00-1.61%) with combined sensory impairments. After adjusting for sociodemographic characteristics, vision impairment (odds ratio (OR) = 1.58, 95% CI = 1.28-1.96) and combined sensory impairments (OR = 1.64, 95% CI = 1.23-2.20) were associated with greater risk of severe to extremely severe dementia. Hearing impairment was not significantly associated with dementia. Sensory impairments are associated with greater risk of dementia in Chinese older adults. Studies are needed to further explore the pathway of this association in Chinese elderly adults and to provide suggestions to improve health status for this population. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

  4. Immunologic Disorders of the Inner Ear.

    ERIC Educational Resources Information Center

    Kinney, William C.; Hughes, Gordon B.

    1997-01-01

    Immune inner ear disease represents a series of immune system mediated problems that can present with hearing loss, dizziness, or both. The etiology, presentation, testing, and treatment of primary immune inner ear disease is discussed. A review of secondary immune inner ear disease is presented for comparison. (Contains references.) (Author/CR)

  5. Perspectives for the treatment of sensorineural hearing loss by cellular regeneration of the inner ear.

    PubMed

    Almeida-Branco, Mario S; Cabrera, Sonia; Lopez-Escamez, Jose A

    2015-01-01

    Sensorineural hearing loss is a caused by the loss of the cochlear hair cells with the consequent deafferentation of spiral ganglion neurons. Humans do not show endogenous cellular regeneration in the inner ear and there is no exogenous therapy that allows the replacement of the damaged hair cells. Currently, treatment is based on the use of hearing aids and cochlear implants that present different outcomes, some difficulties in auditory discrimination and a limited useful life. More advanced technology is hindered by the functional capacity of the remaining spiral ganglion neurons. The latest advances with stem cell therapy and cellular reprogramming have developed several possibilities to induce endogenous regeneration or stem cell transplantation to replace damaged inner ear hair cells and restore hearing function. With further knowledge of the cellular and molecular biology of the inner ear and its embryonic development, it will be possible to use induced stem cells as in vitro models of disease and as replacement cellular therapy. Investigation in this area is focused on generating cellular therapy with clinical use for the treatment of profound sensorineural hearing loss. Copyright © 2014 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

  6. Nutrient-Enhanced Diet Reduces Noise-Induced Damage to the Inner Ear and Hearing Loss

    PubMed Central

    Le Prell, C. G.; Gagnon, P. M; Bennett, D. C.; Ohlemiller, K. K.

    2011-01-01

    Oxidative stress has been broadly implicated as a cause of cell death and neural degeneration in multiple disease conditions; however, the evidence for successful intervention with dietary antioxidant manipulations has been mixed. In this study, we investigated the potential for protection of cells in the inner ear using a dietary supplement with multiple antioxidant components, selected for their potential interactive effectiveness. Protection against permanent threshold shift (PTS) was observed in CBA/J mice maintained on a diet supplemented with a combination of β-carotene, vitamins C and E, and magnesium when compared to PTS in control mice maintained on a nutritionally complete control diet. Although hair cell survival was not enhanced, noise-induced loss of Type II fibrocytes in the lateral wall was significantly reduced (p<0.05), and there was a trend towards less noise-induced loss in strial cell density in animals maintained on the supplemented diet. Taken together, our data suggest that pre-noise oral treatment with the high-nutrient diet can protect cells in the inner ear and reduce PTS in mice. Demonstration of functional and morphological preservation of cells in the inner ear with oral administration of this antioxidant supplemented diet supports the possibility of translation to human patients, and suggests an opportunity to evaluate antioxidant protection in mouse models of oxidative stress-related disease and pathology. PMID:21708355

  7. Processing of simple and complex acoustic signals in a tonotopically organized ear

    PubMed Central

    Hummel, Jennifer; Wolf, Konstantin; Kössl, Manfred; Nowotny, Manuela

    2014-01-01

    Processing of complex signals in the hearing organ remains poorly understood. This paper aims to contribute to this topic by presenting investigations on the mechanical and neuronal response of the hearing organ of the tropical bushcricket species Mecopoda elongata to simple pure tone signals as well as to the conspecific song as a complex acoustic signal. The high-frequency hearing organ of bushcrickets, the crista acustica (CA), is tonotopically tuned to frequencies between about 4 and 70 kHz. Laser Doppler vibrometer measurements revealed a strong and dominant low-frequency-induced motion of the CA when stimulated with either pure tone or complex stimuli. Consequently, the high-frequency distal area of the CA is more strongly deflected by low-frequency-induced waves than by high-frequency-induced waves. This low-frequency dominance will have strong effects on the processing of complex signals. Therefore, we additionally studied the neuronal response of the CA to native and frequency-manipulated chirps. Again, we found a dominant influence of low-frequency components within the conspecific song, indicating that the mechanical vibration pattern highly determines the neuronal response of the sensory cells. Thus, we conclude that the encoding of communication signals is modulated by ear mechanics. PMID:25339727

  8. A different type of 'glue ear': report of an unusual case of prominent ears.

    PubMed

    Purcell, Elizabeth M; O'Neill, Ann C; Regan, Padraic J

    2003-09-01

    Prominent ears is a condition that can cause extreme psychological distress in young people. This cosmetic deformity can be corrected by otoplasty, an outpatient surgical procedure that is associated with a high rate of patient satisfaction. We report the unusual case of a teenage boy who had repeatedly applied cyanoacrylate adhesive ("superglue") to his postauricular skin in an attempt to pin back his prominent ears. This case of "glue ear" was ultimately resolved by successful otoplasty, although the residual effects of the glue resulted in delayed healing of the surgical wound.

  9. What Is an Ear Infection?

    MedlinePlus

    ... Hearing Loss? Taking Care of Your Ears Swimmer's Ear Perforated Eardrum What's Earwax? View ... All information on KidsHealth® is for educational purposes only. For specific medical advice, diagnoses, and treatment, ...

  10. Finite-Element Modelling of the Acoustic Input Admittance of the Newborn Ear Canal and Middle Ear.

    PubMed

    Motallebzadeh, Hamid; Maftoon, Nima; Pitaro, Jacob; Funnell, W Robert J; Daniel, Sam J

    2017-02-01

    Admittance measurement is a promising tool for evaluating the status of the middle ear in newborns. However, the newborn ear is anatomically very different from the adult one, and the acoustic input admittance is different than in adults. To aid in understanding the differences, a finite-element model of the newborn ear canal and middle ear was developed and its behaviour was studied for frequencies up to 2000 Hz. Material properties were taken from previous measurements and estimates. The simulation results were within the range of clinical admittance measurements made in newborns. Sensitivity analyses of the material properties show that in the canal model, the maximum admittance and the frequency at which that maximum admittance occurs are affected mainly by the stiffness parameter; in the middle-ear model, the damping is as important as the stiffness in influencing the maximum admittance magnitude but its effect on the corresponding frequency is negligible. Scaling up the geometries increases the admittance magnitude and shifts the resonances to lower frequencies. The results suggest that admittance measurements can provide more information about the condition of the middle ear when made at multiple frequencies around its resonance.

  11. Ear - blocked at high altitudes

    MedlinePlus

    ... ears; Flying and blocked ears; Eustachian tube dysfunction - high altitude ... to the eardrum) and the back of the nose and upper throat. ... down from high altitudes. Chewing gum the entire time you are ...

  12. Klippel-Feil syndrome and associated ear anomalies.

    PubMed

    Yildirim, Nadir; Arslanoğlu, Atilla; Mahiroğullari, Mahir; Sahan, Murat; Ozkan, Hüseyin

    2008-01-01

    Klippel-Feil syndrome (KFS) is a congenital segmentation anomaly of the cervical vertebrae that manifests as short neck, low hair line, and limited neck mobility. Various systemic malformations may also accompany the syndrome including wide variety of otopathologies affecting all 3 compartments of the ear (external, middle, and inner ear) as well as internal acoustic canal and vestibular aqueduct. We aimed to investigate these involvements and their clinical correlates in a group of patients with KFS. We present 20 KFS cases, of which 12 (% 60) displayed most of the reported ear abnormalities such as microtia, external ear canal stenosis, chronic ear inflammations and their sequels, anomalies of the tympanic cavity and ossicles, inner ear dysplasies, deformed internal acoustic canal, and wide vestibular aqueduct, which are demonstrated using the methods of otoscopy, audiologic testing, and temporal bone computed tomography. This series represents one of the highest reported rate of ear involvement in KFS. We found no correlation between the identified ear pathologies and the skeletal and extraskeletal malformations. The genetic nature of the syndrome was supported by the existence of affected family members in 4 (20%) of the cases.

  13. Transcriptional regulation of cranial sensory placode development

    PubMed Central

    Moody, Sally A.; LaMantia, Anthony-Samuel

    2015-01-01

    Cranial sensory placodes derive from discrete patches of the head ectoderm, and give rise to numerous sensory structures. During gastrulation, a specialized “neural border zone” forms around the neural plate in response to interactions between the neural and non-neural ectoderm and signals from adjacent mesodermal and/or endodermal tissues. This zone subsequently gives rise to two distinct precursor populations of the peripheral nervous system: the neural crest and the pre-placodal ectoderm (PPE). The PPE is a common field from which all cranial sensory placodes arise (adenohypophyseal, olfactory, lens, trigeminal, epibranchial, otic). Members of the Six family of transcription factors are major regulators of PPE specification, in partnership with co-factor proteins such as Eya. Six gene activity also maintains tissue boundaries between the PPE, neural crest and epidermis by repressing genes that specify the fates of those adjacent ectodermally-derived domains. As the embryo acquires anterior-posterior identity, the PPE becomes transcriptionally regionalized, and it subsequently subdivides into specific placodes with distinct developmental fates in response to signaling from adjacent tissues. Each placode is characterized by a unique transcriptional program that leads to the differentiation of highly specialized cells, such as neurosecretory cells, somatic sensory receptor cells, chemosensory neurons, peripheral glia and supporting cells. In this review, we summarize the transcriptional and signaling factors that regulate key steps of placode development, influence subsequent sensory neuron specification, and discuss what is known about mutations in some of the essential PPE genes that underlie human congenital syndromes. PMID:25662264

  14. Ultrastructural study of cytochemical localization of carbonic anhydrase in the inner ear.

    PubMed

    Hsu, C J

    1991-01-01

    Vibratome sections were stained for cytochemical localization of carbonic anhydrase (CA) activity in vestibular neuro-epithelium, spiral ligament and spiral limbus. The new finding is the localization of reaction products in the interdental cells of the spiral limbus, Claudius' cells, mesothelial cells of the lower border of spiral ligament, vestibular sensory cells and perilymphatic cells, which have not earlier been proved to have CA activity. The interdental cells showed the products only on the basolateral infoldings. Claudius' cells showed prominent products in the microvilli. In the vestibular sensory cells, the products were present only in the stereocilia and cuticular areas. The perilymphatic fibrocytes under the vestibular sensory epithelium, like the fibrocytes of the spiral ligament, revealed diffuse products throughout the whole cell. In the vestibular supporting cells and transitional cells, the reaction products were localized diffusely in the cytosol, but not in the secretory granules. In the long cell projections of the transitional cells, type II fibrocytes at spiral prominence, mesothelial cells at the uppermost region of the spiral ligament and Borghesan's zone, the localization of the reaction products was the same as that of the basolateral infoldings of the vestibular dark cells and marginal cells of stria vascularis shown previously.

  15. Comparative inner ear transcriptome analysis between the Rickett's big-footed bats (Myotis ricketti) and the greater short-nosed fruit bats (Cynopterus sphinx).

    PubMed

    Dong, Dong; Lei, Ming; Liu, Yang; Zhang, Shuyi

    2013-12-23

    Bats have aroused great interests of researchers for the sake of their advanced echolocation system. However, this highly specialized trait is not characteristic of Old World fruit bats. To comprehensively explore the underlying molecular basis between echolocating and non-echolocating bats, we employed a sequence-based approach to compare the inner ear expression difference between the Rickett's big-footed bat (Myotis ricketti, echolocating bat) and the Greater short-nosed fruit bat (Cynopterus sphinx, non-echolocating bat). De novo sequence assemblies were developed for both species. The results showed that the biological implications of up-regulated genes in M. ricketti were significantly over-represented in biological process categories such as 'cochlea morphogenesis', 'inner ear morphogenesis' and 'sensory perception of sound', which are consistent with the inner ear morphological and physiological differentiation between the two bat species. Moreover, the expression of TMC1 gene confirmed its important function in echolocating bats. Our work presents the first transcriptome comparison between echolocating and non-echolocating bats, and provides information about the genetic basis of their distinct hearing traits.

  16. Transmission matrix analysis of the chinchilla middle ear

    PubMed Central

    Songer, Jocelyn E.; Rosowski, John J.

    2008-01-01

    Despite the common use of the chinchilla as an animal model in auditory research, a complete characterization of the chinchilla middle ear using transmission matrix analysis has not been performed. In this paper we describe measurements of middle-ear input admittance and stapes velocity in ears with the middle-ear cavity opened under three conditions: intact tympano-ossicular system and cochlea, after the cochlea has been drained, and after the stapes has been fixed. These measurements, made with stimulus frequencies of 100–8000 Hz, are used to define the transmission matrix parameters of the middle ear and to calculate the cochlear input impedance as well as the middle-ear output impedance. This transmission characterization of the chinchilla middle ear will be useful for modeling auditory sensitivity in the normal and pathological chinchilla ear. PMID:17672642

  17. Treating "cauliflower ear" with silicone mold.

    PubMed

    Gross, C G

    1978-01-01

    Acute hematoma of the ear (cauliflower ear) can be satisfactorily treated with aspiration and the use of the silicone mold to prevent reaccumulation of the blood or serum in the ear. Advantages of the silicone mold over other dressings appears to be ease of application, patient acceptance, and prevention of reoccurrence of reaccumulation of the hematoma.

  18. Communication routes between intracranial spaces and inner ear: function, pathophysiologic importance and relations with inner ear diseases.

    PubMed

    Ciuman, Raphael R

    2009-01-01

    There exist 3 communication routes between the intracranial space and the inner ear, the vestibular aqueduct, the cochlear aqueduct, and the internal auditory canal. They possess a key role in inner ear pressure regulation and fluid homeostasis and are related to inner ear diseases. Relevant literature was reviewed, and the current knowledge of the anatomy, physiologic importance, and relations to inner ear diseases were described. Pathologic communication routes such as semicircular canal dehiscence syndrome were highlighted as well. Abnormalities in all 3 communication routes may predispose or be the cause of distinct inner ear pathologic condition and involved in other cochlear and vestibular syndromes, in which their role is not completely clear. The increasing knowledge of the underlying mechanisms encourages promising approaches for possible intervention in the future.

  19. Protecting Mammalian Hair Cells from Aminoglycoside-Toxicity: Assessing Phenoxybenzamine's Potential.

    PubMed

    Majumder, Paromita; Moore, Paulette A; Richardson, Guy P; Gale, Jonathan E

    2017-01-01

    Aminoglycosides (AGs) are widely used antibiotics because of their low cost and high efficacy against gram-negative bacterial infection. However, AGs are ototoxic, causing the death of sensory hair cells in the inner ear. Strategies aimed at developing or discovering agents that protect against aminoglycoside ototoxicity have focused on inhibiting apoptosis or more recently, on preventing antibiotic uptake by the hair cells. Recent screens for ototoprotective compounds using the larval zebrafish lateral line identified phenoxybenzamine as a potential protectant for aminoglycoside-induced hair cell death. Here we used live imaging of FM1-43 uptake as a proxy for aminoglycoside entry, combined with hair-cell death assays to evaluate whether phenoxybenzamine can protect mammalian cochlear hair cells from the deleterious effects of the aminoglycoside antibiotic neomycin. We show that phenoxybenzamine can block FM1-43 entry into mammalian hair cells in a reversible and dose-dependent manner, but pre-incubation is required for maximal inhibition of entry. We observed differential effects of phenoxybenzamine on FM1-43 uptake in the two different types of cochlear hair cell in mammals, the outer hair cells (OHCs) and inner hair cells (IHCs). The requirement for pre-incubation and reversibility suggests an intracellular rather than an extracellular site of action for phenoxybenzamine. We also tested the efficacy of phenoxybenzamine as an otoprotective agent. In mouse cochlear explants the hair cell death resulting from 24 h exposure to neomycin was steeply dose-dependent, with 50% cell death occurring at ~230 μM for both IHC and OHC. We used 250 μM neomycin in subsequent hair-cell death assays. At 100 μM with 1 h pre-incubation, phenoxybenzamine conferred significant protection to both IHCs and OHCs, however at higher concentrations phenoxybenzamine itself showed clear signs of ototoxicity and an additive toxic effect when combined with neomycin. These data do not

  20. The neuroecology of cartilaginous fishes: sensory strategies for survival.

    PubMed

    Collin, Shaun P

    2012-01-01

    line system, the distribution of electroreceptive pores over the head, and the morphology of the inner ear. These results are presented in the context of predictions of sensory capabilities for species living in a range of ecological niches, what further research is needed, and how this sensory input may be a predictor of behavior. Copyright © 2012 S. Karger AG, Basel.

  1. Elliptical-P cells in the avian perilymphatic interface of the Tegmentum vasculosum

    NASA Technical Reports Server (NTRS)

    Fermin, C. D.; Lee, D. H.; Martin, D. S.

    1995-01-01

    Elliptical cells (E-P) are present at the perilymphatic interface lumen (PIL) of the lagena. The E-P cells often separate from the tegmentum vasculosum (TV) and have touching processes that form a monolayer between the K+ rich perilymph and the Na+ rich endolymph, similar to the mammalian Reissner's membrane. We examined the TV of chicks (Gallus domesticus) and quantitated the expression of anti-S100 alphaalphabetabeta and S100 beta. There was a 30% increase of S100 beta saturation in the light cells facing the PIL when compared to other TV light cells. We show that: (1) the dimer anti- S100 alphaalphabetabeta and the monomer anti-S100 beta are expressed preferentially in the light cells and the E-P cells of TV; (2) expression of S100 beta is higher in light cells facing the PIL than in adjacent cells; (3) the expression of the dimer S100 alphaalphabetabeta and monomer S100 beta overlaps in most inner ear cell types, including the cells of the TV, most S100 alphaalphabetabeta positive cells express S 100 beta, but S100 beta positive cells do not always express S100 alphaalphabetabeta; and (4) the S100 beta expression in light cells, the abundant Na+-K+ ATPase on dark cells of the TV, and previously demonstrated co-localization of S100 beta/GABA in sensory cells suggest that S100 beta could have, in the inner ear, a dual neurotrophic-ionic modulating function.

  2. Molecular Mechanisms of Inner Ear Development

    PubMed Central

    Wu, Doris K.; Kelley, Matthew W.

    2012-01-01

    The inner ear is a structurally complex vertebrate organ built to encode sound, motion, and orientation in space. Given its complexity, it is not surprising that inner ear dysfunction is a relatively common consequence of human genetic mutation. Studies in model organisms suggest that many genes currently known to be associated with human hearing impairment are active during embryogenesis. Hence, the study of inner ear development provides a rich context for understanding the functions of genes implicated in hearing loss. This chapter focuses on molecular mechanisms of inner ear development derived from studies of model organisms. PMID:22855724

  3. Molecular mechanisms of inner ear development.

    PubMed

    Wu, Doris K; Kelley, Matthew W

    2012-08-01

    The inner ear is a structurally complex vertebrate organ built to encode sound, motion, and orientation in space. Given its complexity, it is not surprising that inner ear dysfunction is a relatively common consequence of human genetic mutation. Studies in model organisms suggest that many genes currently known to be associated with human hearing impairment are active during embryogenesis. Hence, the study of inner ear development provides a rich context for understanding the functions of genes implicated in hearing loss. This chapter focuses on molecular mechanisms of inner ear development derived from studies of model organisms.

  4. The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells.

    PubMed

    Parker, Andrew; Cross, Sally H; Jackson, Ian J; Hardisty-Hughes, Rachel; Morse, Susan; Nicholson, George; Coghill, Emma; Bowl, Michael R; Brown, Steve D M

    2015-12-01

    Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss. © 2015. Published by The Company of

  5. Middle ear impedance measurements in large vestibular aqueduct syndrome.

    PubMed

    Bilgen, Cem; Kirkim, Günay; Kirazli, Tayfun

    2009-06-01

    To assess the effect of inner ear pressure on middle ear impedance in patients with large vestibular aqueduct syndrome (LVAS). Data from admittance tympanometry and multifrequency tympanometry on 8 LVAS patients and control subjects were studied. Static acoustic compliance (SAC) values for the ears with stable sensorineural hearing loss (SNHL) were within the limits of the mean values of control groups except for two ears. The resonance frequency (RF) values of the ears with stable SNHL were lower than the mean values of control groups except for three ears. SAC values for the two ears with fluctuating SNHL were lower and the RF values were higher than the mean values of control groups. Decreased SAC values and increased RF values found in the ears with fluctuating SNHL might be an indirect indicator of increased inner ear pressure, while low RF values in the ears with stable SNHL might reflect the decreased inner ear impedance.

  6. Deriving the real-ear SPL of audiometric data using the "coupler to dial difference" and the "real ear to coupler difference".

    PubMed

    Munro, K J; Davis, J

    2003-04-01

    The purpose of the study was to compare the measured real-ear sound pressure level (SPL) of audiometer output with the derived real-ear SPL obtained by adding the coupler to dial difference (CDD) and real-ear to coupler difference (RECD) to the audiometer dial reading. The real-ear SPL and RECD were measured in one ear of 16 normally hearing subjects using a probe-tube microphone. The CDD transform and the RECD transfer function were measured in an HA1 and an HA2 2-cc coupler using an EAR-LINK foam ear-tip or a customized earmold. The RECD transfer function was measured using the EARTone ER 3A and the Audioscan RE770 insert earphone. The procedures were very reliable with mean differences on retest of less than 1 dB. The mean difference between the measured and derived real-ear SPL was generally less than 1 dB and rarely exceeded 3 dB in any subject. The CDD measured for an individual audiometer and the RECD measured for an individual ear can be used to derive a valid estimate of real-ear SPL when it has not been possible to measure this directly.

  7. Comparison of Microbiological Flora in the External Auditory Canal of Normal Ear and an Ear with Acute Otitis Externa.

    PubMed

    Ghanpur, Asheesh Dora; Nayak, Dipak Ranjan; Chawla, Kiran; Shashidhar, V; Singh, Rohit

    2017-09-01

    Acute Otitis Externa (AOE) is also known as swimmer's ear. Investigations initiated during World War II firmly established the role of bacteria in the aetiology of Acute Otitis Externa. To culture the microbiological flora of the normal ear and compare it with the flora causing AOE and to know the role of normal ear canal flora and anaerobes in the aetiology. A prospective observational study was conducted on 64 patients clinically diagnosed with unilateral AOE. Ear swabs were taken from both the ears. Microbiological flora was studied considering diseased ear as test ear and the normal ear as the control. Aerobic and anaerobic cultures were done. Severity of the disease was assessed by subjective and objective scores. Effect of topical treatment with ichthammol glycerine pack was assessed after 48 hours and scores were calculated again. Patients with scores < 4 after pack removal were started on systemic antibiotics and were assessed after seven days of antibiotics course. Data was analysed using Paired t-test, Wilcoxon signed ranks test and Chi-square test. A p-value < 0.05 was considered significant. Pseudomonas aeruginosa (33%) was the most common bacteria cultured from the ear followed by Methicillin Resistant Staphylococcus aureus (MRSA) (18%). Patients with anaerobic organism in the test ear had severe symptoms and needed systemic antibiotic therapy. Most of the cases may respond to empirical antibiotic therapy. In cases with severe symptoms and the ones refractory to empirical treatment, a culture from the ear canal will not be a tax on the patient. This helps in giving a better understanding about the disease, causative organisms and helps in avoiding the use of inappropriate antibiotics that usually result in developing resistant strains of bacteria.

  8. An optimal state estimation model of sensory integration in human postural balance

    NASA Astrophysics Data System (ADS)

    Kuo, Arthur D.

    2005-09-01

    We propose a model for human postural balance, combining state feedback control with optimal state estimation. State estimation uses an internal model of body and sensor dynamics to process sensor information and determine body orientation. Three sensory modalities are modeled: joint proprioception, vestibular organs in the inner ear, and vision. These are mated with a two degree-of-freedom model of body dynamics in the sagittal plane. Linear quadratic optimal control is used to design state feedback and estimation gains. Nine free parameters define the control objective and the signal-to-noise ratios of the sensors. The model predicts statistical properties of human sway in terms of covariance of ankle and hip motion. These predictions are compared with normal human responses to alterations in sensory conditions. With a single parameter set, the model successfully reproduces the general nature of postural motion as a function of sensory environment. Parameter variations reveal that the model is highly robust under normal sensory conditions, but not when two or more sensors are inaccurate. This behavior is similar to that of normal human subjects. We propose that age-related sensory changes may be modeled with decreased signal-to-noise ratios, and compare the model's behavior with degraded sensors against experimental measurements from older adults. We also examine removal of the model's vestibular sense, which leads to instability similar to that observed in bilateral vestibular loss subjects. The model may be useful for predicting which sensors are most critical for balance, and how much they can deteriorate before posture becomes unstable.

  9. Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in developing sensory epithelia.

    PubMed

    Weil, D; Levy, G; Sahly, I; Levi-Acobas, F; Blanchard, S; El-Amraoui, A; Crozet, F; Philippe, H; Abitbol, M; Petit, C

    1996-04-16

    The gene encoding human myosin VIIA is responsible for Usher syndrome type III (USH1B), a disease which associates profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. The reconstituted cDNA sequence presented here predicts a 2215 amino acid protein with a typical unconventional myosin structure. This protein is expected to dimerize into a two-headed molecule. The C terminus of its tail shares homology with the membrane-binding domain of the band 4.1 protein superfamily. The gene consists of 48 coding exons. It encodes several alternatively spliced forms. In situ hybridization analysis in human embryos demonstrates that the myosin VIIA gene is expressed in the pigment epithelium and the photoreceptor cells of the retina, thus indicating that both cell types may be involved in the USH1B retinal degenerative process. In addition, the gene is expressed in the human embryonic cochlear and vestibular neuroepithelia. We suggest that deafness and vestibular dysfunction in USH1B patients result from a defect in the morphogenesis of the inner ear sensory cell stereocilia.

  10. Modulatory Role of Sensory Innervation on Hair Follicle Stem Cell Progeny during Wound Healing of the Rat Skin

    PubMed Central

    Martínez-Martínez, Eduardo; Galván-Hernández, Claudio I.; Toscano-Márquez, Brenda; Gutiérrez-Ospina, Gabriel

    2012-01-01

    Background The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing. Methodology/Principal Findings We used neonatal capsaicin treatment to reduce sensory terminals in the rat skin and performed morphometric analyses using design-based stereological methods. Epithelial proliferation was analyzed by quantifying the number of bromodeoxyuridine-labeled (BrdU+) nuclei in the epidermis and hair follicles. After wounding, the epidermis of capsaicin-treated rats presented fewer BrdU+ nuclei than in control rats. To assess SC progeny migration, we employed a double labeling protocol with iododeoxyuridine and chlorodeoxyuridine (IdU+/CldU+). The proportion of double-labeled cells was similar in the hair follicles of both groups at 32 h postwounding. IdU+/CldU+ cell proportion increased in the epidermis of control rats and decreased in treated rats at 61 h postwounding. The epidermal volume immunostained for keratin 6 was greater in treated rats at 61 h. Confocal microscopy analysis revealed that substance P (SP) and calcitonin gene-related peptide (CGRP) receptor immunoreactivity were both present in CD34+ and BrdU-retaining cells of the hair follicles. Conclusions/Significance Our results suggest that capsaicin denervation impairs SC progeny egress from the hair follicles, a circumstance associated with a greater epidermal activation. Altogether, these phenomena would explain the longer times for healing in denervated skin. Thus, sensory innervation

  11. Middle-ear velocity transfer function, cochlear input immittance, and middle-ear efficiency in chinchilla.

    PubMed

    Ravicz, Michael E; Rosowski, John J

    2013-10-01

    The transfer function H(V) between stapes velocity V(S) and sound pressure near the tympanic membrane P(TM) is a descriptor of sound transmission through the middle ear (ME). The ME power transmission efficiency (MEE), the ratio of sound power entering the cochlea to power entering the middle ear, was computed from H(V) measured in seven chinchilla ears and previously reported measurements of ME input admittance Y(TM) and ME pressure gain G(MEP) [Ravicz and Rosowski, J. Acoust. Soc. Am. 132, 2437-2454 (2012); J. Acoust. Soc. Am. 133, 2208-2223 (2013)] in the same ears. The ME was open, and a pressure sensor was inserted into the cochlear vestibule for most measurements. The cochlear input admittance Y(C) computed from H(V) and G(MEP) is controlled by a combination of mass and resistance and is consistent with a minimum-phase system up to 27 kHz. The real part Re{Y(C)}, which relates cochlear sound power to inner-ear sound pressure, decreased gradually with frequency up to 25 kHz and more rapidly above that. MEE was about 0.5 between 0.1 and 8 kHz, higher than previous estimates in this species, and decreased sharply at higher frequencies.

  12. Middle-ear velocity transfer function, cochlear input immittance, and middle-ear efficiency in chinchilla

    PubMed Central

    Ravicz, Michael E.; Rosowski, John J.

    2013-01-01

    The transfer function HV between stapes velocity VS and sound pressure near the tympanic membrane PTM is a descriptor of sound transmission through the middle ear (ME). The ME power transmission efficiency (MEE), the ratio of sound power entering the cochlea to power entering the middle ear, was computed from HV measured in seven chinchilla ears and previously reported measurements of ME input admittance YTM and ME pressure gain GMEP [Ravicz and Rosowski, J. Acoust. Soc. Am. 132, 2437–2454 (2012); J. Acoust. Soc. Am. 133, 2208–2223 (2013)] in the same ears. The ME was open, and a pressure sensor was inserted into the cochlear vestibule for most measurements. The cochlear input admittance YC computed from HV and GMEP is controlled by a combination of mass and resistance and is consistent with a minimum-phase system up to 27 kHz. The real part Re{YC}, which relates cochlear sound power to inner-ear sound pressure, decreased gradually with frequency up to 25 kHz and more rapidly above that. MEE was about 0.5 between 0.1 and 8 kHz, higher than previous estimates in this species, and decreased sharply at higher frequencies. PMID:24116422

  13. Size and Cell Number of the Utricle in kinetotically swimming Fish: A parabolic Aircraft Flight Study

    NASA Astrophysics Data System (ADS)

    Baeuerle, A.; Anken, R.; Baumhauer, N.; Hilbig, R.; Rahmann, H.

    Humans taking part in parabolic aircraft flights (PAFs) may suffer from space motion sickness (SMS, a kinetosis). Since it has been repeatedly shown earlier that some fish of a given batch also reveal a kinetotic behaviour during PAFs (especially so-called spinning movements and looping responses), and due to the homology of the vestibular apparatus among all vertebrates, fish can be used as model systems to investigate the origin of susceptibility to motion sickness. Therefore, we examined the utricular maculae (they are responsible for the internalisation of gravity in teleosteans) of fish swimming kinetotically during the μg-phases in the course of PAFs in comparison with animals from the same batch who swam normally. On the light microscopical level, it was found that the total number of both sensory and supporting cells of the utricular maculae did not differ between kinetotic animals as compared to normally swimming fish. Cell density (sensory and supporting cells/100μm -μm), however, was reduced in kinetotic animals (p<0.0001), which seemed to be due to malformed epithelial cells (increase in cell size) of the kinetotic specimens. Susceptibility to kinetoses may therefore originate in asymmetric inner ear otoliths as has been suggested earlier, but also in genetically predispositioned, malformed sensory epithelia. This work was financially supported by the German Aerospace Center (DLR) e.V. (FKZ: 50 WB 9997).

  14. CT of the ear in Pendred syndrome.

    PubMed

    Goldfeld, Moshe; Glaser, Benjamin; Nassir, Elias; Gomori, John Moshe; Hazani, Elitsur; Bishara, Nassir

    2005-05-01

    To prospectively determine the structural anomalies of the inner ear by using thin-section computed tomography (CT) in an extended family with Pendred syndrome. Ethics committee approved the study, and informed consent was obtained from every patient or from parents of patients under legal age. Twelve patients (three females and nine males aged 7-47 years) with Pendred syndrome (all from the same ethnic isolate and with the same mutation in the PDS gene) were evaluated for inner-ear malformation at thin-section CT. Both ears were evaluated. Presence or absence of interscalar septum between upper and middle turns of the cochlea was evaluated, and vestibule and vestibular aqueduct were examined for enlargement. Modiolus was determined to be present or absent (modiolar deficiency). CT scans were evaluated in consensus by two radiologists (M.G., J.M.G.). All patients had inner ear malformation on both sides. Modiolus was absent and vestibule was enlarged on both sides in all 12 patients. Interscalar septum was absent in 18 (75%) of 24 ears. In eight patients, interscalar septum was absent in both ears, whereas in two patients, it was absent on only one side. Aqueduct was enlarged in 20 (80%) of 24 ears. In nine patients, both ears had enlarged aqueducts, while in two patients, only one side was abnormal. Inner ear malformation is an invariable finding in Pendred syndrome. Modiolus deficiency and vestibular enlargement were the most consistent anomalies in this population with Pendred syndrome. (c) RSNA, 2005.

  15. The ideal ear position in Caucasian females.

    PubMed

    Broer, P Niclas; Thiha, Aung; Ehrl, Denis; Sinno, Sammy; Juran, Sabrina; Szpalski, Caroline; Ng, Reuben; Ninkovic, Milomir; Prantl, Lukas; Heidekrueger, Paul I

    2018-03-01

    Ear position contributes significantly to facial appearance. However, while objective measurements remain the foundation for esthetic evaluations, little is known about how an ear should ideally be positioned regarding its rotational axis. This study aimed to further evaluate whether there exists a universally applicable ideal ear axis, and how sociodemographic factors impact such preferences. An interactive online survey was designed, enabling participants to change the axis of a female model's ear in terms of its forward and backward rotation. The questionnaire was sent out internationally to plastic surgeons and the general public. Demographic data were collected and analysis of variance was used to investigate respective preferences. A total of 1016 responses from 35 different countries (response rate: 18.5%) were gathered. Overall, 60% of survey takers chose the minus 10 or 5° angles to be most attractive. Significant differences were found regarding sex, ethnicity, country of residence, profession and respective ear axis preferences. Across multiple countries and ethnicities, an ear position in slight reclination of minus 5-10° is considered most pleasing in Caucasian females. However, sociodemographic factors significantly impact individual ear axis preferences and should be taken into consideration when performing reconstructive ear surgery. Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  16. Evolution of Gravity Receptors in the Ear

    NASA Technical Reports Server (NTRS)

    Popper, Arthur N. (Principal Investigator)

    1996-01-01

    The general status of a grant to investigate the origins and evolution of two hair cell types in the ears of a teleost fish, Astronotus ocellatus (the oscar), is presented. First, it was demonstrated that the cells in the rostral end of the saccule of the , Carassius auratus, are type 1-like, while those at the caudal end are type 2 cells. It was demonstrated that the dichotomy of hair cell types found in the utricle of the oscar is also found in the goldfish. Second, the lateral line system of the oscar was examined using gentamicin sulphate, an ototocix drug that destroys type 1- like hair cells but does not appear to damage type 2 hair cells. It was demonstrated that the hair cells found in neuromasts of lateral line canal organs were totally destroyed within 1 day of treatment, while the hair cells in free neuromasts were undamaged after 12 days of treatment. Third, it was demonstrated that the calyx, the specialized nerve ending, is not unique to amniotes and that it is present at least in the cristae of semicirular canals in goldfish. These results have demonstrated that: (1) there are multiple hair cell types in the vestibular endorgans of the ear of fishes, (2) these hair cell types are very similar to those found in the mammalian vestibular endorgans, (3) the nerve calyx is also present in fishes, and (4) multiple hair cell types and the calyx have evolved far earlier in the course of vertebrate evolution than heretofore thought. Understanding the structure of the vestibular endorgans has important implications for being able to understand how these organs respond to gravistatic, acceleration and acoustic input. The vestibular endorgans of fishes may provide an ideal system in which to analyze functional differences in hair cells. Not only are the two hair cell types similar to those found in mammals, they are located in very discrete regions in each endorgan. Thus, it is relatively easy to gain access to cells of one or the other type. The presence of two

  17. Numerical analysis of ossicular chain lesion of human ear

    NASA Astrophysics Data System (ADS)

    Liu, Yingxi; Li, Sheng; Sun, Xiuzhen

    2009-04-01

    Lesion of ossicular chain is a common ear disease impairing the sense of hearing. A comprehensive numerical model of human ear can provide better understanding of sound transmission. In this study, we propose a three-dimensional finite element model of human ear that incorporates the canal, tympanic membrane, ossicular bones, middle ear suspensory ligaments/muscles, middle ear cavity and inner ear fluid. Numerical analysis is conducted and employed to predict the effects of middle ear cavity, malleus handle defect, hypoplasia of the long process of incus, and stapedial crus defect on sound transmission. The present finite element model is shown to be reasonable in predicting the ossicular mechanics of human ear.

  18. [Constricted ear therapy with free auricular composite grafts].

    PubMed

    Liu, Tun; Zhang, Lian-sheng; Zhuang, Hong-xing; Zhang, Ke-yuan

    2004-03-01

    A simple and effective therapy for single side constricted ear. Transplanting normal side free composite auricular grafts to constricted ear (15 patients and 15 sides), then lengthening the helix, exposing the scapha, correcting deformity. The 15 patients composite grafts all survived. The helix has been lengthened, the scapha exposed, the normal ear reduced, the constricted ear augmented and two sides ear have become symmetry. This method is simple and results are satisfied.

  19. Hair cell ribbon synapses

    PubMed Central

    Brandt, Andreas; Lysakowski, Anna

    2010-01-01

    Hearing and balance rely on the faithful synaptic coding of mechanical input by the auditory and vestibular hair cells of the inner ear. Mechanical deflection of their stereocilia causes the opening of mechanosensitive channels, resulting in hair cell depolarization, which controls the release of glutamate at ribbon-type synapses. Hair cells have a compact shape with strong polarity. Mechanoelectrical transduction and active membrane turnover associated with stereociliar renewal dominate the apical compartment. Transmitter release occurs at several active zones along the basolateral membrane. The astonishing capability of the hair cell ribbon synapse for temporally precise and reliable sensory coding has been the subject of intense investigation over the past few years. This research has been facilitated by the excellent experimental accessibility of the hair cell. For the same reason, the hair cell serves as an important model for studying presynaptic Ca2+ signaling and stimulus-secretion coupling. In addition to common principles, hair cell synapses differ in their anatomical and functional properties among species, among the auditory and vestibular organs, and among hair cell positions within the organ. Here, we briefly review synaptic morphology and connectivity and then focus on stimulus-secretion coupling at hair cell synapses. PMID:16944206

  20. Innate immune recognition of molds and homology to the inner ear protein, cochlin, in patients with autoimmune inner ear disease

    PubMed Central

    Pathak, Shresh; Hatam, Lynda J.; Bonagura, Vincent; Vambutas, Andrea

    2013-01-01

    Autoimmune Inner Ear Disease (AIED) is characterized by bilateral, fluctuating sensorineural hearing loss with periods of hearing decline triggered by unknown stimuli. Here we examined whether an environmental exposure to mold in these AIED patients is sufficient to generate a pro-inflammatory response that may, in part, explain periods of acute exacerbation of disease. We hypothesized that molds may stimulate an aberrant immune response in these patients as both several Aspergillus species and penecillium share homology with the LCCL domain of the inner ear protein, cochlin. We showed the presence of higher levels of anti-mold IgG in plasma of AIED patients at dilution of 1:256 (p=0.032) and anti-cochlin IgG 1:256 (p=0.0094 and at 1:512 p=0.024) as compared with controls. Exposure of peripheral blood mononuclear cells (PBMC) of AIED patients to mold resulted in an up-regulation of IL-1β mRNA expression, enhanced IL-1β and IL-6 secretion, and generation of IL-17 expressing cells in mold-sensitive AIED patients, suggesting mold acts as a PAMP in a subset of these patients. Naïve B cells secreted IgM when stimulated with conditioned supernatant from AIED patients’ monocytes treated with mold extract. In conclusion, the present studies indicate that fungal exposure can trigger autoimmunity in a subset of susceptible AIED patients. PMID:23912888

  1. Facial Asymmetry: Brow and Ear Position.

    PubMed

    Perumal, Balaji; Meyer, Dale R

    2018-04-01

    The purpose of the current study was to analyze brow and ear position, and examine the relationship between these structures in patients presenting for blepharoplasty evaluation. A retrospective chart review was performed, which included all patients presenting to one oculoplastic physician for a blepharoplasty evaluation from November, 2012 to March, 2014. The prevalence of brow ptosis and brow and ear asymmetry was calculated; the proportional distribution was determined, and chi-square analysis and the z-test of proportions were used to calculate the significance. Institutional Review Board approval was obtained for this study. A total of 133 patients met the inclusion criteria. Some degree of brow ptosis was noted in 83% of patients. Brow asymmetry was found in 88% of patients, and ear asymmetry in 77%. Of those patients who had asymmetry, 61% had the right brow lower and 75% had the right ear lower; 73% of all patients had the brow and ear lower on the same side ( p  < 0.001). In this study, brow ptosis and asymmetry were quite common. In addition, the side of the lower brow correlated strongly with the side of the lower ear, and the right side structures were lower more often than the left. Patients presenting for blepharoplasty evaluation may have an element of generalized facial asymmetry which includes the brows and ears. These observations can be important for preoperative planning and patient counseling. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Biometric recognition using 3D ear shape.

    PubMed

    Yan, Ping; Bowyer, Kevin W

    2007-08-01

    Previous works have shown that the ear is a promising candidate for biometric identification. However, in prior work, the preprocessing of ear images has had manual steps and algorithms have not necessarily handled problems caused by hair and earrings. We present a complete system for ear biometrics, including automated segmentation of the ear in a profile view image and 3D shape matching for recognition. We evaluated this system with the largest experimental study to date in ear biometrics, achieving a rank-one recognition rate of 97.8 percent for an identification scenario and an equal error rate of 1.2 percent for a verification scenario on a database of 415 subjects and 1,386 total probes.

  3. The role of intracochlear drug delivery devices in the management of inner ear disease.

    PubMed

    Ayoob, Andrew M; Borenstein, Jeffrey T

    2015-03-01

    Diseases of the inner ear include those of the auditory and vestibular systems, and frequently result in disabling hearing loss or vertigo. Despite a rapidly expanding pipeline of potential cochlear therapeutics, the inner ear remains a challenging organ for targeted drug delivery, and new technologies are required to deliver these therapies in a safe and efficacious manner. In addition to traditional approaches for direct inner ear drug delivery, novel microfluidics-based systems are under development, promising improved control over pharmacokinetics over longer periods of delivery, ultimately with application towards hair cell regeneration in humans. Advances in the development of intracochlear drug delivery systems are reviewed, including passive systems, active microfluidic technologies and cochlear prosthesis-mediated delivery. This article provides a description of novel delivery systems and their potential future clinical applications in treating inner ear disease. Recent progresses in microfluidics and miniaturization technologies are enabling the development of wearable and ultimately implantable drug delivery microsystems. Progress in this field is being spurred by the convergence of advances in molecular biology, microfluidic flow control systems and models for drug transport in the inner ear. These advances will herald a new generation of devices, with near-term applications in preclinical models, and ultimately with human clinical use for a range of diseases of the inner ear.

  4. Impact of Staphylococcus epidermidis lysates on middle ear epithelial proinflammatory and mucogenic response.

    PubMed

    Val, Stéphanie; Mubeen, Humaira; Tomney, Amarel; Chen, Saisai; Preciado, Diego

    2015-02-01

    Chronic otitis media with effusion (COME) develops after sustained inflammation and is characterized by secretory middle ear epithelial metaplasia and effusion, most frequently mucoid. Staphylococcus epidermidis, typically considered a commensal organism, is very frequently recovered in chronic middle ear fluid and in middle ear biofilms. Although it has been shown to drive inflammation in sinonasal epithelium, the impact of S. epidermidis on COME is markedly understudied. The goal of this study was to examine the in vitro effects of S. epidermidis lysates on murine and human middle ear epithelial cells. Staphylococcus epidermidis lysates were generated and used to stimulate submerged and differentiated human and murine epithelial cells (MEECs) for 24 to 48 hours. Quantitative real time-polymerase chain reaction, Western blot, enzyme-linked immunosorbent assay, and immunocytochemistry techniques were performed to interrogate the mucin gene MUC5AC and MUC5B expression and protein production, chemokine response, as well as NF-κB activation. Luciferase reporter assays were performed to further evaluate nuclear factor κB (NF-κB) activation and query specific promoter responses after S. epidermidis exposure. Staphylococcus epidermidis induced a time- and dose-dependent MUC5AC and MUC5B overexpression along with a parallel overexpression of Cxcl2 in mouse MEEC and IL-8 in human MEEC. Further investigations in mMEEC showed a 1.3 to 1.5 induction of the MUC5AC and MUC5B promoters. As potential mechanisms for these responses, induction of an oxidative stress marker, along with early nuclear translocation and activation of NF-κB, was found. Finally, chronic exposure induced marked epithelial thickening of cells differentiated at the air liquid interface. Staphylococcus epidermidis lysates activate a proinflammatory response in MEEC, including mucin gene expression and protein production. Although typically considered a nonpathogenic commensal organism in the ear, these

  5. Acceleration induced water removal from ear canals.

    NASA Astrophysics Data System (ADS)

    Kang, Hosung; Averett, Katelee; Jung, Sunghwan

    2017-11-01

    Children and adults commonly experience having water trapped in the ear canals after swimming. To remove the water, individuals will shake their head sideways. Since a child's ear canal has a smaller diameter, it requires more acceleration of the head to remove the trapped water. In this study, we theoretically and experimentally investigated the acceleration required to break the surface meniscus of the water in artificial ear canals and hydrophobic-coated glass tubes. In experiments, ear canal models were 3D-printed from a CT-scanned human head. Also, glass tubes were coated with silane to match the hydrophobicity in ear canals. Then, using a linear stage, we measured the acceleration values required to forcefully eject the water from the artificial ear canals and glass tubes. A theoretical model was developed to predict the critical acceleration at a given tube diameter and water volume by using a modified Rayleigh-Taylor instability. Furthermore, this research can shed light on the potential of long-term brain injury and damage by shaking the head to push the water out of the ear canal. This research was supported by National Science Foundation Grant CBET-1604424.

  6. Fgf10 is required for specification of non-sensory regions of the cochlear epithelium

    PubMed Central

    Urness, Lisa D.; Wang, Xiaofen; Shibata, Shumei; Ohyama, Takahiro; Mansour, Suzanne L.

    2015-01-01

    The vertebrate inner ear is a morphologically complex sensory organ comprised of two compartments, the dorsal vestibular apparatus and the ventral cochlear duct, required for motion and sound detection, respectively. Fgf10, in addition to Fgf3, is necessary for the earliest stage of otic placode induction, but continued expression of Fgf10 in the developing otic epithelium, including the prosensory domain and later in Kolliker’s organ, suggests additional roles for this gene during morphogenesis of the labyrinth. While loss of Fgf10 was implicated previously in semicircular canal agenesis, we show that Fgf10−/+ embryos also exhibit a reduction or absence of the posterior semicircular canal, revealing a dosage-sensitive requirement for FGF10 in vestibular development. In addition, we show that Fgf10−/− embryos have previously unappreciated defects of cochlear morphogenesis, including a somewhat shortened duct, and, surprisingly, a substantially narrower duct. The mutant cochlear epithelium lacks Reissner’s membrane and a large portion of the outer sulcus--two non-contiguous, non-sensory domains. Marker gene analyses revealed effects on Reissner’s membrane as early as E12.5–E13.5 and on the outer sulcus by E15.5, stages when Fgf10 is expressed in close proximity to Fgfr2b, but these effects were not accompanied by changes in epithelial cell proliferation or death. These data indicate a dual role for Fgf10 in cochlear development: to regulate outgrowth of the duct and subsequently as a bidirectional signal that sequentially specifies Reissner’s membrane and outer sulcus non-sensory domains. These findings may help to explain the hearing loss sometimes observed in LADD syndrome subjects with FGF10 mutations. PMID:25624266

  7. Convergence of Cortical and Sensory Driver Inputs on Single Thalamocortical Cells

    PubMed Central

    Groh, Alexander; Bokor, Hajnalka; Mease, Rebecca A.; Plattner, Viktor M.; Hangya, Balázs; Stroh, Albrecht; Deschenes, Martin; Acsády, László

    2014-01-01

    Ascending and descending information is relayed through the thalamus via strong, “driver” pathways. According to our current knowledge, different driver pathways are organized in parallel streams and do not interact at the thalamic level. Using an electron microscopic approach combined with optogenetics and in vivo physiology, we examined whether driver inputs arising from different sources can interact at single thalamocortical cells in the rodent somatosensory thalamus (nucleus posterior, POm). Both the anatomical and the physiological data demonstrated that ascending driver inputs from the brainstem and descending driver inputs from cortical layer 5 pyramidal neurons converge and interact on single thalamocortical neurons in POm. Both individual pathways displayed driver properties, but they interacted synergistically in a time-dependent manner and when co-activated, supralinearly increased the output of thalamus. As a consequence, thalamocortical neurons reported the relative timing between sensory events and ongoing cortical activity. We conclude that thalamocortical neurons can receive 2 powerful inputs of different origin, rather than only a single one as previously suggested. This allows thalamocortical neurons to integrate raw sensory information with powerful cortical signals and transfer the integrated activity back to cortical networks. PMID:23825316

  8. Classification and Current Management of Inner Ear Malformations.

    PubMed

    Sennaroğlu, Levent; Bajin, Münir Demir

    2017-09-29

    Morphologically congenital sensorineural hearing loss can be investigated under two categories. The majority of congenital hearing loss causes (80%) are membranous malformations. Here, the pathology involves inner ear hair cells. There is no gross bony abnormality and, therefore, in these cases high-resolution computerized tomography and magnetic resonance imaging of the temporal bone reveal normal findings. The remaining 20% have various malformations involving the bony labyrinth and, therefore, can be radiologically demonstrated by computerized tomography and magnetic resonance imaging. The latter group involves surgical challenges as well as problems in decision-making. Some cases may be managed by a hearing aid, others need cochlear implantation, and some cases are candidates for an auditory brainstem implantation (ABI). During cochlear implantation, there may be facial nerve abnormalities, cerebrospinal fluid leakage, electrode misplacement or difficulty in finding the cochlea itself. During surgery for inner ear malformations, the surgeon must be ready to modify the surgical approach or choose special electrodes for surgery. In the present review article, inner ear malformations are classified according to the differences observed in the cochlea. Hearing and language outcomes after various implantation methods are closely related to the status of the cochlear nerve, and a practical classification of the cochlear nerve deficiency is also provided.

  9. Membrane potential correlates of sensory perception in mouse barrel cortex.

    PubMed

    Sachidhanandam, Shankar; Sreenivasan, Varun; Kyriakatos, Alexandros; Kremer, Yves; Petersen, Carl C H

    2013-11-01

    Neocortical activity can evoke sensory percepts, but the cellular mechanisms remain poorly understood. We trained mice to detect single brief whisker stimuli and report perceived stimuli by licking to obtain a reward. Pharmacological inactivation and optogenetic stimulation demonstrated a causal role for the primary somatosensory barrel cortex. Whole-cell recordings from barrel cortex neurons revealed membrane potential correlates of sensory perception. Sensory responses depended strongly on prestimulus cortical state, but both slow-wave and desynchronized cortical states were compatible with task performance. Whisker deflection evoked an early (<50 ms) reliable sensory response that was encoded through cell-specific reversal potentials. A secondary late (50-400 ms) depolarization was enhanced on hit trials compared to misses. Optogenetic inactivation revealed a causal role for late excitation. Our data reveal dynamic processing in the sensory cortex during task performance, with an early sensory response reliably encoding the stimulus and later secondary activity contributing to driving the subjective percept.

  10. Passage of albumin from the middle ear to the inner ear in otitis media in the chinchilla

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Goldberg, B.; Goycoolea, M.V.; Schleivert, P.M.

    1981-08-01

    A study of the permeability of the middle ear-inner ear interface for macromolecules was carried out in chinchillas with open and obstructed eustachian tubes utilizing tritiated human serum albumin and immunoelectrophoresis. Tritiated albumin was placed in the round window niche area or normal animals and animals in which the eustachian tubes had been obstructed for 24 hours or 14 days. The tritiated albumin was allowed to remain in the middle ear cavity for 24 hours, Samples of middle ear effusion, perilymph, blood and cerebrospinal fluid were collected and measured for radioactivity. Radioactivity was demonstrated in the perilymph. Samples of middlemore » ear effusions and perilymph were also studied by immunoelectrophoresis with goat antihuman albumin. Albumin placed in the round window niche of an experimental animal could be recovered unchanged in the perilymph. The results suggest a pathophysiologic explanation for the association of otitis media and sensorineural hearing loss or endolymphatic hydrops.« less

  11. Fly-ear inspired acoustic sensors for gunshot localization

    NASA Astrophysics Data System (ADS)

    Liu, Haijun; Currano, Luke; Gee, Danny; Yang, Benjamin; Yu, Miao

    2009-05-01

    The supersensitive ears of the parasitoid fly Ormia ochracea have inspired researchers to develop bio-inspired directional microphone for sound localization. Although the fly ear is optimized for localizing the narrow-band calling song of crickets at 5 kHz, experiments and simulation have shown that it can amplify directional cues for a wide frequency range. In this article, a theoretical investigation is presented to study the use of fly-ear inspired directional microphones for gunshot localization. Using an equivalent 2-DOF model of the fly ear, the time responses of the fly ear structure to a typical shock wave are obtained and the associated time delay is estimated by using cross-correlation. Both near-field and far-field scenarios are considered. The simulation shows that the fly ear can greatly amplify the time delay by ~20 times, which indicates that with an interaural distance of only 1.2 mm the fly ear is able to generate a time delay comparable to that obtained by a conventional microphone pair with a separation as large as 24 mm. Since the parameters of the fly ear structure can also be tuned for muzzle blast and other impulse stimulus, fly-ear inspired acoustic sensors offers great potential for developing portable gunshot localization systems.

  12. Incorporating anthropometry into design of ear-related products.

    PubMed

    Liu, Bor-Shong

    2008-01-01

    To achieve mass customization and collaborative product design, human factors and ergonomics should play a key development role. The purpose of this study was to provide product designers with the anthropometic dimensions of outer ears for different demographic data, including gender and age. The second purpose was to compare the dimensions of various ear-related products (i.e., earphone, bluetooth earphone and ear-cup earphone) with the anthropometic database and recommend appropriate solutions for design. Two hundred subjects aged 20-59 was selected for this study and divided into four age stratifications. Further, three different dimensions of the outer ear (i.e., the earhole length, the ear connection length and the length of the pinna) were measured by superimposed grid photographic technique. The analysis of variance (ANOVA) was used to investigate the effects of gender, and age on ear dimensions. The results showed that all ear dimensions had significant gender effects. A comparison between the anthropometric dimensions and those of current products revealed that most current ear-related products need to be redesigned using anthropometric data. The shapes of earhole and pinna are not circular. Consequently, ear products need to be elongated so that users may feel more comfortably and not have the product slip off easily.

  13. Immunohistochemical localization of serotonin and choline acetyltransferase in sensory neurones of the locust.

    PubMed

    Lutz, E M; Tyrer, N M

    1988-01-15

    Sensory neuronal cell bodies in the leg of locust, Schistocerca gregaria, were visualized with antibodies to locust choline acetyltransferase and with antibodies to serotonin by the avidin-biotin peroxidase technique. Two groups of sensory cells react with the antibody to choline acetyltransferase: One group is associated with external mechanoreceptors (i.e., hair-plate hairs and campaniform sensilla) and the other with internal proprioceptors (i.e., chordotonal organs and multiterminal receptors). Sensory cells which react with the antibody to serotonin are associated only with internal proprioceptors being found in both chordotonal organs and multiterminal receptors. In the metathoracic femoral chordotonal organ indirect evidence suggests that some sensory cells are reactive to both antibodies. Some multiterminal receptors react with anti-choline-acetyltransferase, while others react with antiserotonin. These results support the conclusion that most insect sensory neurones are cholinergic but some are serotoninergic.

  14. Pinna abnormalities and low-set ears

    MedlinePlus

    ... Pinna abnormalities; Genetic defect - pinna; Congenital defect - pinna Images Ear abnormalities Pinna of the newborn ear References Haddad J, Keesecker S. Congenital malformations. In: Kliegman RM, Stanton BF, ...

  15. Induction of differentiation of human embryonic stem cells into functional hair-cell-like cells in the absence of stromal cells.

    PubMed

    Ding, Jie; Tang, Zihua; Chen, Jiarong; Shi, Haosong; Chen, Jianling; Wang, Cuicui; Zhang, Cui; Li, Liang; Chen, Ping; Wang, Jinfu

    2016-12-01

    Sensorineural hearing loss and vestibular dysfunction have become the most common forms of sensory defects. Stem cell-based therapeutic strategies for curing hearing loss are being developed. Several attempts to develop hair cells by using chicken utricle stromal cells as feeder cells have resulted in phenotypic conversion of stem cells into inner ear hair-cell-like cells. Here, we induced the differentiation of human embryonic stem cells (hESCs) into otic epithelial progenitors (OEPs), and further induced the differentiation of OEPs into hair-cell-like cells using different substrates. Our results showed that OEPs cultured on the chicken utricle stromal cells with the induction medium could differentiate into hair-cell-like cells with stereociliary bundles. Co-culture with stromal cells, however, may be problematic for subsequent examination of the induced hair-cell-like cells. In order to avoid the interference from stromal cells, we cultured OEPs on laminin with different induction media and examined the effects of the induction medium on the differentiation potentials of OEPs into hair-cell-like cells. The results revealed that the culture of OEPs on laminin with the conditioned medium from chicken utricle stromal cells supplemented with EGF and all-trans retinoic acid (RA) could promote the organization of cells into epithelial clusters displaying hair-cell-like cells with stereociliary bundles. These cells also displayed the expected electrophysiological properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Localization of efferent neurotransmitters in the inner ear of the homozygous Bronx waltzer mutant mouse.

    PubMed

    Kong, W J; Scholtz, A W; Hussl, B; Kammen-Jolly, K; Schrott-Fischer, A

    2002-05-01

    Naturally occurring mutant mice provide an excellent model for the study of genetic malformations of the inner ear. Mice homozygous for the Bronx waltzer (bv/bv) mutation are severely hearing impaired or deaf and exhibit a 'waltzing' gait. Functional aspects of cochlear and vestibular efferents in the bv/bv mutant mouse are not well known. The present study was designed to evaluate several candidates of efferent neurotransmitters or neuromodulators including choline acetyltransferase (ChAT), gamma-aminobutyric acid (GABA), and calcitonin gene-related peptide (CGRP) in the inner ear of the bv/bv mutant mouse. Ultrastructural investigations at both light and electron microscopic level were performed. Ultrastructural morphologic evaluations of the cochlea and the vestibular end-organs were also undertaken. It is demonstrated that ChAT, GABA and CGRP immunoreactivities are present in the cochlea and in vestibular end-organs of bv/bv mutant mice. In the organ of Corti, immunoreactivity of ChAT, GABA and CGRP is confined to the inner spiral fibers, tunnel-crossing fibers, and the vesiculated nerve endings synapsing with outer hair cells. Interestingly, immunoreactivity was detectable even where inner hair cells appeared missing. Results also revealed malformations of the outer hair cells with synaptic contacts to efferent nerve endings consistently intact. In the neurosensory epithelia of the vestibular end-organs, the presence of ChAT, GABA, and CGRP immunoreactivity was localized at the vestibular efferents, with the exception of the macula of saccule. In one 8-month-old macula of utricle where the depletion of hair cells appeared highest, ChAT immunostaining was still discernible. Ultrastructural investigation demonstrated that vesiculated efferent nerve endings make synaptic contact with the outer hair cells in the organ of Corti and with type II hair cells in the vestibular end-organs. The present study provides further support that the efferent system in the bv

  17. Antibodies Mediate Formation of Neutrophil Extracellular Traps in the Middle Ear and Facilitate Secondary Pneumococcal Otitis Media

    PubMed Central

    Short, Kirsty R.; von Köckritz-Blickwede, Maren; Langereis, Jeroen D.; Chew, Keng Yih; Job, Emma R.; Armitage, Charles W.; Hatcher, Brandon; Fujihashi, Kohtaro; Reading, Patrick C.; Hermans, Peter W.

    2014-01-01

    Otitis media (OM) (a middle ear infection) is a common childhood illness that can leave some children with permanent hearing loss. OM can arise following infection with a variety of different pathogens, including a coinfection with influenza A virus (IAV) and Streptococcus pneumoniae (the pneumococcus). We and others have demonstrated that coinfection with IAV facilitates the replication of pneumococci in the middle ear. Specifically, we used a mouse model of OM to show that IAV facilitates the outgrowth of S. pneumoniae in the middle ear by inducing middle ear inflammation. Here, we seek to understand how the host inflammatory response facilitates bacterial outgrowth in the middle ear. Using B cell-deficient infant mice, we show that antibodies play a crucial role in facilitating pneumococcal replication. We subsequently show that this is due to antibody-dependent neutrophil extracellular trap (NET) formation in the middle ear, which, instead of clearing the infection, allows the bacteria to replicate. We further demonstrate the importance of these NETs as a potential therapeutic target through the transtympanic administration of a DNase, which effectively reduces the bacterial load in the middle ear. Taken together, these data provide novel insight into how pneumococci are able to replicate in the middle ear cavity and induce disease. PMID:24191297

  18. The core planar cell polarity gene prickle interacts with flamingo to promote sensory axon advance in the Drosophila embryo.

    PubMed

    Mrkusich, Eli M; Flanagan, Dustin J; Whitington, Paul M

    2011-10-01

    The atypical cadherin Drosophila protein Flamingo and its vertebrate homologues play widespread roles in the regulation of both dendrite and axon growth. However, little is understood about the molecular mechanisms that underpin these functions. Whereas flamingo interacts with a well-defined group of genes in regulating planar cell polarity, previous studies have uncovered little evidence that the other core planar cell polarity genes are involved in regulation of neurite growth. We present data in this study showing that the planar cell polarity gene prickle interacts with flamingo in regulating sensory axon advance at a key choice point - the transition between the peripheral nervous system and the central nervous system. The cytoplasmic tail of the Flamingo protein is not required for this interaction. Overexpression of another core planar cell polarity gene dishevelled produces a similar phenotype to prickle mutants, suggesting that this gene may also play a role in regulation of sensory axon advance. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  19. Single-stage autologous ear reconstruction for microtia.

    PubMed

    Kasrai, Leila; Snyder-Warwick, Alison K; Fisher, David M

    2014-03-01

    The authors have been using the Nagata technique since 2002. In this review of 100 consecutive ear reconstructions, the authors present technique modifications that have evolved over this period that have contributed to improved auricular contour and that now allow for auricular reconstruction in a single stage. This study is a retrospective review of a prospectively acquired database. The series is restricted to primary reconstructions performed for congenital microtia. Photographs of 10 consecutive patients are presented to demonstrate the results of the technique. Surgical complication rates are discussed. One hundred ear reconstructions were performed in 96 patients. There were 75 primary cases of congenital microtia. Twenty-four ears underwent a two-stage reconstruction, and 51 ears were reconstructed with a Nagata stage I procedure or a single-stage reconstruction. There was a gradual shift in technique, with a trend to perform fewer Nagata stage II outsetting procedures and more single-stage reconstructions. In patients who underwent an ear reconstruction in two stages, the surgical complication rate was 22 percent. In the last 40 consecutive ear reconstructions since abandoning the two-stage approach, the surgical complication rate is now 15 percent. A modification of Nagata's technique of autologous ear reconstruction for microtia is described. Modifications of the three-dimensional framework address the contour of the inferior crus and control tragal projection and position. Inclusion of a projection block and recruitment of retroauricular skin allow for symmetric projection of the ear in a single stage. Therapeutic, IV.

  20. Roles of autolysin and pneumolysin in middle ear inflammation caused by a type 3 Streptococcus pneumoniae strain in the chinchilla otitis media model.

    PubMed Central

    Sato, K; Quartey, M K; Liebeler, C L; Le, C T; Giebink, G S

    1996-01-01

    Streptococcus pneumoniae cell wall and pneumolysin are important contributors to pneumococcal pathogenicity in some animal models. To further explore these factors in middle ear inflammation caused by pneumococci, penicillin-induced inflammatory acceleration was studied by using three closely related pneumococcal strains: a wild-type 3 strain (WT3), its pneumolysin-negative derivative (P-1), and into autolysin-negative derivative (A-1). Both middle ears of chinchillas were inoculated with one of the three pneumococcal strains. During the first 12 h, all three strains grew in vivo at the same rate, and all three strains induced similar inflammatory cell responses in middle ear fluid (MEF). Procaine penicillin G was given as 12 h to one-half of the animals in each group, and all treated chinchillas had sterile MEF at 24 h. Penicillin significantly accelerated MEF inflammatory cell influx into WT3-and P-1-infected ears at 18 and 24 h in comparison with the rate for penicillin-treated A-1-infected ears. Inflammatory cell influx was slightly, but not significantly, greater after treatment of WT3 infection than after treatment of P-1 infection. Interleukin (IL)-1beta and IL-6, but not IL-8, concentrations in MEF at 24 h reflected the penicillin effect on MEF inflammatory cells; however, differences between treatment groups were not significant. Results suggest that pneumococcal otitis media pathogenesis is triggered principally by the inflammatory effects of intact and lytic cell wall products in the middle ear, with at most a modes additional pneumolysin effect. Investigation strategies that limit the release of these products or neutralize them warrant further investigation. PMID:8606070

  1. Audiometric Predictions Using SFOAE and Middle-Ear Measurements

    PubMed Central

    Ellison, John C.; Keefe, Douglas H.

    2006-01-01

    Objective The goals of the study are to determine how well stimulus-frequency otoacoustic emissions (SFOAEs) identify hearing loss, classify hearing loss as mild or moderate-severe, and correlate with pure-tone thresholds in a population of adults with normal middle-ear function. Other goals are to determine if middle-ear function as assessed by wideband acoustic transfer function (ATF) measurements in the ear canal account for the variability in normal thresholds, and if the inclusion of ATFs improves the ability of SFOAEs to identify hearing loss and predict pure-tone thresholds. Design The total suppressed SFOAE signal and its corresponding noise were recorded in 85 ears (22 normal ears and 63 ears with sensorineural hearing loss) at octave frequencies from 0.5 – 8 kHz using a nonlinear residual method. SFOAEs were recorded a second time in three impaired ears to assess repeatability. Ambient-pressure ATFs were obtained in all but one of these 85 ears, and were also obtained from an additional 31 normal-hearing subjects in whom SFOAE data were not obtained. Pure-tone air-and bone-conduction thresholds and 226-Hz tympanograms were obtained on all subjects. Normal tympanometry and the absence of air-bone gaps were used to screen subjects for normal middle-ear function. Clinical decision theory was used to assess the performance of SFOAE and ATF predictors in classifying ears as normal or impaired, and linear regression analysis was used to test the ability of SFOAE and ATF variables to predict the air-conduction audiogram. Results The ability of SFOAEs to classify ears as normal or hearing impaired was significant at all test frequencies. The ability of SFOAEs to classify impaired ears as either mild or moderate-severe was significant at test frequencies from 0.5 to 4 kHz. SFOAEs were present in cases of severe hearing loss. SFOAEs were also significantly correlated with air-conduction thresholds from 0.5 to 8 kHz. The best performance occurred using the SFOAE

  2. Transfection using hydroxyapatite nanoparticles in the inner ear via an intact round window membrane in chinchilla

    NASA Astrophysics Data System (ADS)

    Wu, Xuewen; Ding, Dalian; Jiang, Haiyan; Xing, Xiaowei; Huang, Suping; Liu, Hong; Chen, Zhedong; Sun, Hong

    2012-01-01

    Hydroxyapatite nanoparticles (nHAT) are known to have excellent biocompatibility, and have attracted increasing attention as new candidates of non-viral vectors for gene therapy. In our previous studies, nHAT carrying a therapeutic gene and a reporter gene were successfully transfected into the spiral ganglion neurons in the inner ear of guinea pigs in vivo as well as in the cultured cell lines, although the transfection efficiencies were never higher than 30%. In this study, the surface modification of nHAT with polyethylenimine (PEI) was made (PEI-nHAT, diameter = 73.09 ± 27.32 nm) and a recombinant plasmid carrying enhanced green fluorescent protein (EGFP) gene and neurotrophin-3 (NT-3) gene was constructed as pEGFPC2-NT3. The PEI modified nHAT and the recombinant plasmid was then connected to form the nHAT-based vector-gene complex (PEI-nHAT-pEGFPC2-NT3). This complex was then placed onto the intact round window membranes of the chinchillas for inner ear transfection. Auditory brainstem response (ABR) was tested to evaluate auditory function. Green fluorescence of EGFP was observed using confocal microscopy 48 h after administering vector-gene complexes. There was no significant threshold shift in tone burst-evoked ABR at any tested frequency. Abundant, condensed green fluorescence was found in dark cells on both sides of the crista and around the macula of the utricle. Scattered EGFP signals were also detected in vestibular hair cells, some Schwann cells in the cochlear spiral ganglion region, some outer pillar cells in the organ of Corti, and a few cells in the stria vascularis. The density of green fluorescence-marked cells was obviously higher in the vestibular dark cell area than in other areas of the inner ear, suggesting that vestibular dark cells may have the ability to actively engulf the nHAT-based vector-gene complexes. Considering the high transfection efficiency in the vestibular system, PEI-nHAT may be a potential vector for gene therapy of inner

  3. Comparative analysis of ear-hole closure identifies epimorphic regeneration as a discrete trait in mammals

    PubMed Central

    Gawriluk, Thomas R.; Simkin, Jennifer; Thompson, Katherine L.; Biswas, Shishir K.; Clare-Salzler, Zak; Kimani, John M.; Kiama, Stephen G.; Smith, Jeramiah J.; Ezenwa, Vanessa O.; Seifert, Ashley W.

    2016-01-01

    Why mammals have poor regenerative ability has remained a long-standing question in biology. In regenerating vertebrates, injury can induce a process known as epimorphic regeneration to replace damaged structures. Using a 4-mm ear punch assay across multiple mammalian species, here we show that several Acomys spp. (spiny mice) and Oryctolagus cuniculus completely regenerate tissue, whereas other rodents including MRL/MpJ ‘healer' mice heal similar injuries by scarring. We demonstrate ear-hole closure is independent of ear size, and closure rate can be modelled with a cubic function. Cellular and genetic analyses reveal that injury induces blastema formation in Acomys cahirinus. Despite cell cycle re-entry in Mus musculus and A. cahirinus, efficient cell cycle progression and proliferation only occurs in spiny mice. Together, our data unite blastema-mediated regeneration in spiny mice with regeneration in other vertebrates such as salamanders, newts and zebrafish, where all healthy adults regenerate in response to injury. PMID:27109826

  4. An Effective 3D Ear Acquisition System

    PubMed Central

    Liu, Yahui; Lu, Guangming; Zhang, David

    2015-01-01

    The human ear is a new feature in biometrics that has several merits over the more common face, fingerprint and iris biometrics. It can be easily captured from a distance without a fully cooperative subject. Also, the ear has a relatively stable structure that does not change much with the age and facial expressions. In this paper, we present a novel method of 3D ear acquisition system by using triangulation imaging principle, and the experiment results show that this design is efficient and can be used for ear recognition. PMID:26061553

  5. An Effective 3D Ear Acquisition System.

    PubMed

    Liu, Yahui; Lu, Guangming; Zhang, David

    2015-01-01

    The human ear is a new feature in biometrics that has several merits over the more common face, fingerprint and iris biometrics. It can be easily captured from a distance without a fully cooperative subject. Also, the ear has a relatively stable structure that does not change much with the age and facial expressions. In this paper, we present a novel method of 3D ear acquisition system by using triangulation imaging principle, and the experiment results show that this design is efficient and can be used for ear recognition.

  6. Indolent anti-Hu-associated paraneoplastic sensory neuropathy.

    PubMed

    Graus, F; Bonaventura, I; Uchuya, M; Valls-Solé, J; Reñé, R; Leger, J M; Tolosa, E; Delattre, J Y

    1994-12-01

    Paraneoplastic sensory neuropathy (PSN) usually runs a subacute progressive course, leaving the patient with severe sensory dysfunction in weeks to months. We describe five patients with PSN, high titers of anti-Hu antibodies (type 1 antineuronal nuclear autoantibodies), and an indolent clinical course. The patients had a median age of 55 years (range, 41 to 72). Four had small-cell (3) or undifferentiated large-cell (1) lung cancer. Patients presented with mild, asymmetric sensory symptoms; in two, the neuropathy was predominant in the arms. Two patients also had a visceral neuropathy causing gastrointestinal dysfunction. The PSN was stable or progressed very slowly without treatment for a median of 18 months (range, 5 to 32) and remained so after treatment with immunoglobulins (1 patient), chemotherapy (3), or both therapies (1). All patients were ambulatory, leading an independent life up until the time of the last visit or until death from the tumor (2 patients). The median follow-up was 36 months (range, 22 to 52). A paraneoplastic origin should be considered in patients with mild, very slowly progressive sensory neuropathies.

  7. Optimal Electromechanical Reshaping of the Auricular Ear and Long-term Outcomes in an In Vivo Rabbit Model

    PubMed Central

    Manuel, Cyrus T.; Tjoa, Tjoson; Nguyen, Tony; Su, Erica; Wong, Brian J. F.

    2016-01-01

    IMPORTANCE The prominent ear is a common external ear anomaly that is usually corrected through surgery. Electromechanical reshaping (EMR) may provide the means to reshape cartilage through the use of direct current (in milliamperes) applied percutaneously with needle electrodes and thus to reduce reliance on open surgery. OBJECTIVE To determine the long-term outcomes (shape change, cell viability, and histology) of a more refined EMR voltage and time settings for reshaping rabbit auricle. DESIGN, SETTING, AND SUBJECTS The intact ears of 14 New Zealand white rabbits were divided into 2 groups. Group 1 received 4 V for 5 minutes (5 ears), 5 V for 4 minutes (5 ears), or no voltage for 5 minutes (control; 4 ears). Group 2 received an adjusted treatment of 4 V for 4 minutes (7 ears) or 5 V for 3 minutes (7 ears). A custom mold with platinum electrodes was used to bend the pinna and to perform EMR. Pinnae were splinted for 6 months along the region of the bend. Rabbits were killed humanely and the ears were harvested the day after splint removal. Data were collected from March 14, 2013, to July 8, 2014, and analyzed from August 29, 2013, to March 1, 2015. MAIN OUTCOMES AND MEASURES Bend angle and mechanical behavior via palpation were recorded through photography and videography. Tissue was sectioned for histologic examination and confocal microscopy to assess changes to microscopic structure and cell viability. RESULTS Rabbits ranged in age from 6 to 8 months and weighed 3.8 to 4.0 g. The mean (SD) bend angles were 81° (45°) for the controls and, in the 5 EMR groups, 72° (29°) for 4 V for 4 minutes, 101° (19°) for 4 V for 5 minutes, 78° (18°) for 5 V for 3 minutes, and 126° (21°) for 5 V for 4 minutes. At 5 V, an increase in application time from 3 to 4 minutes provided significant shape change (78° [18°] and 126° [21°], respectively; P = .003). Pinnae stained with hematoxylin-eosin displayed localized areas of cell injury and fibrosis in and around

  8. Gene-expression analysis of hair cell regeneration in the zebrafish lateral line

    PubMed Central

    Jiang, Linjia; Romero-Carvajal, Andres; Haug, Jeff S.; Seidel, Christopher W.; Piotrowski, Tatjana

    2014-01-01

    Deafness caused by the terminal loss of inner ear hair cells is one of the most common sensory diseases. However, nonmammalian animals (e.g., birds, amphibians, and fish) regenerate damaged hair cells. To understand better the reasons underpinning such disparities in regeneration among vertebrates, we set out to define at high resolution the changes in gene expression associated with the regeneration of hair cells in the zebrafish lateral line. We performed RNA-Seq analyses on regenerating support cells purified by FACS. The resulting expression data were subjected to pathway enrichment analyses, and the differentially expressed genes were validated in vivo via whole-mount in situ hybridizations. We discovered that cell cycle regulators are expressed hours before the activation of Wnt/β-catenin signaling following hair cell death. We propose that Wnt/β-catenin signaling is not involved in regulating the onset of proliferation but governs proliferation at later stages of regeneration. In addition, and in marked contrast to mammals, our data clearly indicate that the Notch pathway is significantly down-regulated shortly after injury, thus uncovering a key difference between the zebrafish and mammalian responses to hair cell injury. Taken together, our findings lay the foundation for identifying differences in signaling pathway regulation that could be exploited as potential therapeutic targets to promote either sensory epithelium or hair cell regeneration in mammals. PMID:24706903

  9. Nociceptive Sensory Fibers Drive Interleukin-23 Production from CD301b+ Dermal Dendritic Cells and Drive Protective Cutaneous Immunity.

    PubMed

    Kashem, Sakeen W; Riedl, Maureen S; Yao, Chen; Honda, Christopher N; Vulchanova, Lucy; Kaplan, Daniel H

    2015-09-15

    Innate resistance to Candida albicans in mucosal tissues requires the production of interleukin-17A (IL-17A) by tissue-resident cells early during infection, but the mechanism of cytokine production has not been precisely defined. In the skin, we found that dermal γδ T cells were the dominant source of IL-17A during C. albicans infection and were required for pathogen resistance. Induction of IL-17A from dermal γδ T cells and resistance to C. albicans required IL-23 production from CD301b(+) dermal dendritic cells (dDCs). In addition, we found that sensory neurons were directly activated by C. albicans. Ablation of sensory neurons increased susceptibility to C. albicans infection, which could be rescued by exogenous addition of the neuropeptide CGRP. These data define a model in which nociceptive pathways in the skin drive production of IL-23 by CD301b(+) dDCs resulting in IL-17A production from γδ T cells and resistance to cutaneous candidiasis. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Ear Infection in Isolated Cleft Lip: Etiological Implications

    PubMed Central

    Ruegg, Teresa A.; Cooper, Margaret E.; Leslie, Elizabeth J.; Ford, Matthew D.; Wehby, George L.; Deleyiannis, Frederic W.B.; Czeizel, Andrew E.; Hecht, Jacqueline T.; Marazita, Mary L.; Weinberg, Seth M.

    2015-01-01

    Background and Hypothesis Chronic ear infections are a common occurrence in children with orofacial clefts involving the secondary palate. Less is known about the middle ear status of individuals with isolated clefts of the lip, although several studies have reported elevated rates of ear infection in this group. The purpose of this retrospective study was to test the hypothesis that chronic ear infections occur more frequently in isolated cleft lip cases (n=94) compared with controls (n=183). Methods A questionnaire was used to obtain information on history of chronic ear infection. The association between ear infection status (present/absent) and cleft lip status (cleft lip case/control) was tested using both chi-square and logistic regression. Results and Conclusions The reported occurrence of chronic ear infection was significantly greater in cleft lipcases (31%) compared to unaffected controls (11%). After adjusting for age and sex, having a cleft lip increased the odds of being positive for ear infection by a factor greater than three (OR=3.698; 95%CI=1.91–7.14). Within cleft lipcases, there was no difference in the occurrence of ear infection by defect laterality or by the type of clefting present in the family history. Although velopharyngeal insufficiency was present in 18.4% of our cleft lip sample, there was no statistical association between ear infection and abnormal speech patterns. These results may have potential implications both for the clinical management of isolated cleft lip cases and for understanding the etiology of orofacial clefting. PMID:26153759

  11. Ear Infection in Isolated Cleft Lip: Etiological Implications.

    PubMed

    Ruegg, Teresa A; Cooper, Margaret E; Leslie, Elizabeth J; Ford, Matthew D; Wehby, George L; Deleyiannis, Frederic W B; Czeizel, Andrew E; Hecht, Jacqueline T; Marazita, Mary L; Weinberg, Seth M

    2017-03-01

      Chronic ear infections are a common occurrence in children with orofacial clefts involving the secondary palate. Less is known about the middle ear status of individuals with isolated clefts of the lip, although several studies have reported elevated rates of ear infection in this group. The purpose of this retrospective study was to test the hypothesis that chronic ear infections occur more frequently in isolated cleft lip cases (n = 94) compared with controls (n = 183).   A questionnaire was used to obtain information on history of chronic ear infection. The association between ear infection status (present/absent) and cleft lip status (cleft lip case/control) was tested using both chi-square and logistic regression.   The reported occurrence of chronic ear infection was significantly greater in cleft lip cases (31%) compared with unaffected controls (11%). After adjusting for age and sex, having a cleft lip increased the odds of being positive for ear infection by a factor greater than 3 (odds ratio = 3.698; 95% confidence interval = 1.91 to 7.14). Within cleft lip cases, there was no difference in the occurrence of ear infection by defect laterality or by the type of clefting present in the family history. Although velopharyngeal insufficiency was present in 18.4% of our cleft lip sample, there was no statistical association between ear infection and abnormal speech patterns. These results may have potential implications both for the clinical management of isolated cleft lip cases and for understanding the etiology of orofacial clefting.

  12. A ‘calcium capacitor’ shapes cholinergic inhibition of cochlear hair cells

    PubMed Central

    Fuchs, Paul Albert

    2014-01-01

    Efferent cholinergic neurons project from the brainstem to inhibit sensory hair cells of the vertebrate inner ear. This inhibitory synapse combines the activity of an unusual class of ionotropic cholinergic receptor with that of nearby calcium-dependent potassium channels to shunt and hyperpolarize the hair cell. Postsynaptic calcium signalling is constrained by a thin near-membrane cistern that is co-extensive with the efferent terminal contacts. The postsynaptic cistern may play an essential role in calcium homeostasis, serving as sink or source, depending on ongoing activity and the degree of buffer saturation. Release of calcium from postsynaptic stores leads to a process of retrograde facilitation via the synthesis of nitric oxide in the hair cell. Activity-dependent synaptic modification may contribute to changes in hair cell innervation that occur during development, and in the aged or damaged cochlea. PMID:24566542

  13. Ear tag

    MedlinePlus

    ... an ear tag or pit are: An inherited tendency to have this facial feature A genetic syndrome ... Elsevier Churchill Livingstone; 2016:chap 19. Review Date 4/24/2017 Updated by: Liora C Adler, MD, ...

  14. Ear Infections

    MedlinePlus

    ... but they are less common. The infection usually affects the middle ear and is called otitis media. ... become clogged with fluid and mucus. This can affect hearing, because sound cannot get through all that ...

  15. Ear emergencies

    MedlinePlus

    ... and ruptured eardrums can be caused by: Inserting cotton swabs, toothpicks, pins, pens, or other objects into ... The person will have severe pain. Place sterile cotton gently in the outer ear canal to keep ...

  16. Neuroglial modulation in peripheral sensory systems.

    PubMed

    Pack, Adam K; Pawson, Lorraine J

    2010-08-01

    Glia are increasingly appreciated as active participants in central neural processing via calcium waves, electrical coupling, and even synaptic-like release of "neuro"-transmitters. In some sensory organs (e.g., retina, olfactory bulb), glia have been shown to interact with neurons in the same manner, although their role in perception has yet to be elucidated. In the organ of Corti, synapses occur between supporting cells and neurons. In one sensory organ, the Pacinian corpuscle (fine touch), glia have been shown to play just as important a role in sensory transduction as they do in neural processing in the brain, and the functional role is quite clear; the modified Schwann cells of the capsule are responsible for the rapid adaptation process of the PCs, integral to its function as a vibration detector. This complex glial/neuronal relationship may be a recent evolutionary phenomenon and may account for much of the relative sophistication of vertebrate nervous systems.

  17. NOD2/RICK-Dependent β-Defensin 2 Regulation Is Protective for Nontypeable Haemophilus influenzae-Induced Middle Ear Infection

    PubMed Central

    Woo, Jeong-Im; Oh, Sejo; Webster, Paul; Lee, Yoo Jin; Lim, David J.; Moon, Sung K.

    2014-01-01

    Middle ear infection, otitis media (OM), is clinically important due to the high incidence in children and its impact on the development of language and motor coordination. Previously, we have demonstrated that the human middle ear epithelial cells up-regulate β-defensin 2, a model innate immune molecule, in response to nontypeable Haemophilus influenzae (NTHi), the most common OM pathogen, via TLR2 signaling. NTHi does internalize into the epithelial cells, but its intracellular trafficking and host responses to the internalized NTHi are poorly understood. Here we aimed to determine a role of cytoplasmic pathogen recognition receptors in NTHi-induced β-defensin 2 regulation and NTHi clearance from the middle ear. Notably, we observed that the internalized NTHi is able to exist freely in the cytoplasm of the human epithelial cells after rupturing the surrounding membrane. The human middle ear epithelial cells inhibited NTHi-induced β-defensin 2 production by NOD2 silencing but augmented it by NOD2 over-expression. NTHi-induced β-defensin 2 up-regulation was attenuated by cytochalasin D, an inhibitor of actin polymerization and was enhanced by α-hemolysin, a pore-forming toxin. NOD2 silencing was found to block α-hemolysin-mediated enhancement of NTHi-induced β-defensin 2 up-regulation. NOD2 deficiency appeared to reduce inflammatory reactions in response to intratympanic inoculation of NTHi and inhibit NTHi clearance from the middle ear. Taken together, our findings suggest that a cytoplasmic release of internalized NTHi is involved in the pathogenesis of NTHi infections, and NOD2-mediated β-defensin 2 regulation contributes to the protection against NTHi-induced otitis media. PMID:24625812

  18. LOSS OF SESTRIN 2 POTENTIATES THE EARLY ONSET OF AGE-RELATED SENSORY CELL DEGENERATION IN THE COCHLEA

    PubMed Central

    ZHANG, CELIA; SUN, WEI; LI, JI; XIONG, BINBIN; FRYE, MITCHELL D.; DING, DALIAN; SALVI, RICHARD; KIM, MI-JUNG; SOMEYA, SHINICHI; HU, BO HUA

    2017-01-01

    Sestrin 2 (SESN2) is a stress-inducible protein that protects tissues from oxidative stress and delays the aging process. However, its role in maintaining the functional and structural integrity of the cochlea is largely unknown. Here, we report the expression of SESN2 protein in the sensory epithelium, particularly in hair cells. Using C57BL/6J mice, a mouse model of age-related cochlear degeneration, we observed a significant age-related reduction in SESN2 expression in cochlear tissues that was associated with early onset hearing loss and accelerated age-related sensory cell degeneration that progressed from the base toward the apex of the cochlea. Hair cell death occurred by caspase-8 mediated apoptosis. Compared to C57BL/6J control mice, Sesn2 KO mice displayed enhanced expression of proinflammatory genes and activation of basilar membrane macrophages, suggesting that loss of SESN2 function provokes the immune response. Together, these results suggest that Sesn2 plays an important role in cochlear homeostasis and immune responses to stress. PMID:28818524

  19. Age-Related Sensory Impairments and Risk of Cognitive Impairment.

    PubMed

    Fischer, Mary E; Cruickshanks, Karen J; Schubert, Carla R; Pinto, Alex A; Carlsson, Cynthia M; Klein, Barbara E K; Klein, Ronald; Tweed, Ted S

    2016-10-01

    To evaluate the associations between sensory impairments and 10-year risk of cognitive impairment. The Epidemiology of Hearing Loss Study (EHLS), a longitudinal, population-based study of aging in the Beaver Dam, Wisconsin community. Baseline examinations were conducted in 1993 and follow-up examinations have been conducted every 5 years. General community. EHLS members without cognitive impairment at EHLS-2 (1998-2000). There were 1,884 participants (mean age 66.7) with complete EHLS-2 sensory data and follow-up information. Cognitive impairment was defined as a Mini-Mental State Examination score of <24 or history of dementia or Alzheimer's disease. Hearing impairment was a pure-tone average of hearing thresholds (0.5, 1, 2, 4 kHz) of >25 dB hearing level in either ear, visual impairment was a Pelli-Robson contrast sensitivity of <1.55 log units in the better eye, and olfactory impairment was a San Diego Odor Identification Test score of <6. Hearing, visual, and olfactory impairment were independently associated with cognitive impairment risk (hearing: hazard ratio (HR) = 1.90, 95% confidence interval (CI) = 1.11-3.26; vision: HR = 2.05, 95% CI = 1.24-3.38; olfaction: HR = 3.92, 95% CI = 2.45-6.26)). Nevertheless, 85% of participants with hearing impairment, 81% with visual impairment, and 76% with olfactory impairment did not develop cognitive impairment during follow-up. The relationship between sensory impairment and cognitive impairment was not unique to one sensory system, suggesting that sensorineural health may be a marker of brain aging. The development of a combined sensorineurocognitive measure may be useful in uncovering mechanisms of healthy brain aging. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  20. Management of auricular hematoma and the cauliflower ear.

    PubMed

    Greywoode, Jewel D; Pribitkin, Edmund A; Krein, Howard

    2010-12-01

    Acute auricular hematoma is common after blunt trauma to the side of the head. A network of vessels provides a rich blood supply to the ear, and the ear cartilage receives its nutrients from the overlying perichondrium. Prompt management of hematoma includes drainage and prevention of reaccumulation. If left untreated, an auricular hematoma can result in complications such as perichondritis, infection, and necrosis. Cauliflower ear may result from long-standing loss of blood supply to the ear cartilage and formation of neocartilage from disrupted perichondrium. Management of cauliflower ear involves excision of deformed cartilage and reshaping of the auricle. © Thieme Medical Publishers.

  1. Effects of Varieties, Producing Areas, Ears, and Ear Positions of Single Maize Kernels on Near-Infrared Spectra for Identification and Traceability.

    PubMed

    An, Dong; Cui, Yongjin; Liu, Xu; Jia, Shiqiang; Zheng, Shuyun; Che, Xiaoping; Liu, Zhe; Zhang, Xiaodong; Zhu, Dehai; Li, Shaoming

    2016-01-01

    The effects of varieties, producing areas, ears, and ear positions of maize on near-infrared (NIR) spectra were investigated to determine the factors causing the differences in NIR fingerprints of maize varieties. A total of 130 inbred lines were grown in two regions in China, and 12,350 kernel samples were analyzed through NIR spectroscopy. Spectral differences among varieties, producing areas, ears, and ear positions were determined and compared on the basis of pretreated spectra. The bands at 1300-1470, 1768-1949, 2010-2064, and 2235-2311 nm were mainly affected by the producing area. Band selection and principal component analysis were applied to improve the influence of variety on NIR spectra by processing the pretreated spectra. The degrees of the influence of varieties, producing areas, ears, and ear positions were calculated, and the percentages of the influence of varieties, producing areas, ears, and ear positions were 45.40%, 42.66%, 8.22%, and 3.72%, respectively. Therefore, genetic differences among maize inbred lines are the main factors accounted for NIR spectral differences. Producing area is a secondary factor. These results could provide a reference for researchers who authenticate varieties, perform geographical origin traceabilities, and conduct maize seed breeding.

  2. Regulation of T-type Ca2+ channel expression by herpes simplex virus-1 infection in sensory-like ND7 cells

    PubMed Central

    Zhang, Qiaojuan; Hsia, Shao-Chung

    2017-01-01

    Infection of sensory neurons by herpes simplex virus (HSV)-1 disrupts electrical excitability, altering pain sensory transmission. Because of their low threshold for activation, functional expression of T-type Ca2+ channels regulates various cell functions, including neuronal excitability and neuronal communication. In this study, we have tested the effect of HSV-1 infection on the functional expression of T-type Ca2+ channels in differentiated ND7-23 sensory-like neurons. Voltage-gated Ca2+ currents were measured using whole cell patch clamp recordings in differentiated ND7-23 neurons under various culture conditions. Differentiation of ND7-23 cells evokes a significant increase in T-type Ca2+ current densities. Increased T-type Ca2+ channel expression promotes the morphological differentiation of ND7-23 cells and triggers a rebound depolarization. HSV-1 infection of differentiated ND7-23 cells causes a significant loss of T-type Ca2+ channels from the membrane. HSV-1 evoked reduction in the functional expression of T-type Ca2+ channels is mediated by several factors, including decreased expression of Cav3.2 T-type Ca2+ channel subunits and disruption of endocytic transport. Decreased functional expression of T-type Ca2+ channels by HSV-1 infection requires protein synthesis and viral replication, but occurs independently of Egr-1 expression. These findings suggest that infection of neuron-like cells by HSV-1 causes a significant disruption in the expression of T-type Ca2+ channels, which can results in morphological and functional changes in electrical excitability. PMID:28639215

  3. Pierced Ears

    MedlinePlus

    ... weeks. Then you can start enjoying your pierced ears again! Reviewed by: Steven Dowshen, MD Date reviewed: September ... All information on KidsHealth® is for educational purposes only. For specific medical advice, diagnoses, and treatment, ...

  4. Fumonisin B(1)-nonproducing strains of Fusarium verticillioides cause maize (Zea mays) ear infection and ear rot.

    PubMed

    Desjardins, A E; Plattner, R D

    2000-11-01

    Fumonisins are polyketide mycotoxins produced by Fusarium verticillioides (synonym F. moniliforme), a major pathogen of maize (Zea mays) worldwide. Most field strains produce high levels of fumonisin B(1) (FB(1)) and low levels of the less-oxygenated homologues FB(2) and FB(3), but fumonisin B(1)-nonproducing field strains have been obtained by natural variation. To test the role of various fumonisins in pathogenesis on maize under field conditions, one strain producing FB(1), FB(2), and FB(3), one strain producing only FB(2), one strain producing only FB(3), and one fumonisin-nonproducing strain were applied to ears via the silk channel and on seeds at planting. Disease severity on the harvested ears was evaluated by visible symptoms and by weight percent symptomatic kernels. Fumonisin levels in kernels were determined by high-performance liquid chromatography. The presence of the applied FB(1)-nonproducing strains in kernels was determined by analysis of recovered strains for fumonisin production and other traits. All three FB(1)-nonproducing strains were able to infect ears following either silk-channel application or seed application at planting and were as effective as the FB(1)-producing strain in causing ear rot following silk-channel application. These results indicate that production of FB(1), FB(2), or FB(3) is not required for F. verticillioides to cause maize ear infection and ear rot.

  5. Computational Modeling of Blast Wave Transmission Through Human Ear.

    PubMed

    Leckness, Kegan; Nakmali, Don; Gan, Rong Z

    2018-03-01

    Hearing loss has become the most common disability among veterans. Understanding how blast waves propagate through the human ear is a necessary step in the development of effective hearing protection devices (HPDs). This article presents the first 3D finite element (FE) model of the human ear to simulate blast wave transmission through the ear. The 3D FE model of the human ear consisting of the ear canal, tympanic membrane, ossicular chain, and middle ear cavity was imported into ANSYS Workbench for coupled fluid-structure interaction analysis in the time domain. Blast pressure waveforms recorded external to the ear in human cadaver temporal bone tests were applied at the entrance of the ear canal in the model. The pressure waveforms near the tympanic membrane (TM) in the canal (P1) and behind the TM in the middle ear cavity (P2) were calculated. The model-predicted results were then compared with measured P1 and P2 waveforms recorded in human cadaver ears during blast tests. Results show that the model-derived P1 waveforms were in an agreement with the experimentally recorded waveforms with statistic Kurtosis analysis. The FE model will be used for the evaluation of HPDs in future studies.

  6. Anthropometric growth study of the ear in a Chinese population.

    PubMed

    Zhao, Shichun; Li, Dianguo; Liu, Zhenzhong; Wang, Yibiao; Liu, Lei; Jiang, Duyin; Pan, Bo

    2018-04-01

    A large number of anthropometric studies of the auricle have been reported in different nations, but little data were available in the Chinese population. The aim of this study was to analyze growth changes in the ear by measuring the width and length of ears in a Chinese population. A total of 480 participants were enrolled and classified into 1-, 3-, 5-, 7-, 9-, 12-, 14-, and 18-year groups (half were boys and half were girls in each group). Ear length, ear width, body weight, and body length were measured and recorded; ear index was calculated according to ear length and ear width. The growth of auricle and differences between genders were analyzed. Growth of ear in relation to body height and weight and the degree of emphasis on the length and width of the auricle were also analyzed. Ear length and width increased with age. Ear length achieved its mature size in both 14-year-old males and females. Ear width reached its mature size in males at 7 years and in females at 5 years. Different trends of ear index were shown between males and females. People in this population paid more attention to the length than the width of the auricle. The data indicated that ear development followed increase in age. There were gender and ethnic difference in the development of ear. These results may have potential implications for the diagnosis of congenital malformations, syndromes, and planning of ear reconstruction surgery. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  7. Effect of electronic cigarettes on human middle ear.

    PubMed

    Song, Jae-Jun; Go, Yoon Young; Mun, Ji Yoen; Lee, Sehee; Im, Gi Jung; Kim, Yoo Yon; Lee, Jun Ho; Chang, Jiwon

    2018-06-01

    Electronic cigarettes (e-cigarettes) are the most commonly used electronic nicotine delivery systems and are a relatively new product designed for smoking cessation. The market scale of electronic cigarettes is growing rapidly, but the potential impact of e-cigarettes on public health has not yet been verified. In this study, we examined the effect of e-liquids on a human middle ear epithelial cell (HMEEC) line. The main components of e-liquids are propylene glycol, vegetable glycerin and flavoring agents with or without nicotine. We analyzed 73 bottles of e-liquids from 12 different manufacturers, evaluated the trace elements in e-liquids, and identified the cytotoxicity of e-liquids on HMEECs in the presence or absence of nicotine. In the trace elements analysis, nickel, arsenic, cadmium, and lead were detected in the e-liquids. E-liquids without nicotine decreased cell viability, and the average IC 50 value of total e-liquids (n = 73) was 2.48 ± 0.93%. Among the different flavors, menthol-flavored e-liquids significantly reduced cell viability, and their average IC 50 value (n = 28) was 1.85 ± 0.80%. The average IC 50 values were distinct among manufacturers and the proportion of the solvents. The present study provides evidence that e-cigarettes influence and reduce human middle ear cell viability even without the application of nicotine. Additionally, the cytotoxicity of e-liquids was affected by the flavoring agents. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Inner ear dysfunction in caspase-3 deficient mice

    PubMed Central

    2011-01-01

    Background Caspase-3 is one of the most downstream enzymes activated in the apoptotic pathway. In caspase-3 deficient mice, loss of cochlear hair cells and spiral ganglion cells coincide closely with hearing loss. In contrast with the auditory system, details of the vestibular phenotype have not been characterized. Here we report the vestibular phenotype and inner ear anatomy in the caspase-3 deficient (Casp3-/-) mouse strain. Results Average ABR thresholds of Casp3-/- mice were significantly elevated (P < 0.05) compared to Casp3+/- mice and Casp3+/+ mice at 3 months of age. In DPOAE testing, distortion product 2F1-F2 was significantly decreased (P < 0.05) in Casp3-/- mice, whereas Casp3+/- and Casp3+/+ mice showed normal and comparable values to each other. Casp3-/- mice were hyperactive and exhibited circling behavior when excited. In lateral canal VOR testing, Casp3-/- mice had minimal response to any of the stimuli tested, whereas Casp3+/- mice had an intermediate response compared to Casp3+/+ mice. Inner ear anatomical and histological analysis revealed gross hypomorphism of the vestibular organs, in which the main site was the anterior semicircular canal. Hair cell numbers in the anterior- and lateral crista, and utricle were significantly smaller in Casp3-/- mice whereas the Casp3+/- and Casp3+/+ mice had normal hair cell numbers. Conclusions These results indicate that caspase-3 is essential for correct functioning of the cochlea as well as normal development and function of the vestibule. PMID:21988729

  9. Musical ear syndrome in adult cochlear implant patients.

    PubMed

    Low, W-K; Tham, C A; D'Souza, V-D; Teng, S-W

    2013-09-01

    Except for a single case report, musical ear syndrome in cochlear implantees has not been studied. We aimed to study the prevalence and nature of musical ear syndrome among adult cochlear implant patients, as well as the effect on their emotional well-being. STUDY DESIGN, PATIENTS AND INTERVENTION: A cross-sectional survey of patients aged 18 years and above who had received cochlear implants for profound hearing loss between 1997 and 2010. Of the 82 patients studied, 18 (22 per cent) were found to have experienced musical ear syndrome. Seven and 11 patients had musical ear syndrome prior to and after cochlear implantation, respectively. The character of musical ear syndrome symptoms was described as instrumental music (n = 2), singing (6) or both (10). Fourteen patients reported an adverse emotional effect, with three expressing ‘intolerance’. In this study, 22 per cent of cochlear implantees experienced musical ear syndrome. These symptoms affected patients’ emotional state, but most coped well. Musical ear syndrome can occur prior to and after cochlear implantation.

  10. [Adaptability of sweet corn ears to a frozen process].

    PubMed

    Ramírez Matheus, Alejandra O; Martínez, Norelkys Maribel; de Bertorelli, Ligia O; De Venanzi, Frank

    2004-12-01

    The effects of frozen condition on the quality of three sweet corn ears (2038, 2010, 2004) and the pattern (Bonanza), were evaluated. Biometrics characteristics like ear size, ear diameter, row and kernel deep were measured as well as chemical and physical measurement in fresh and frozen states. The corn ears were frozen at -95 degrees C by 7 minutes. The yield and stability of the frozen ears were evaluated at 45 and 90 days of frozen storage (-18 degrees C). The average commercial yield as frozen corn ear for all the hybrids was 54.2%. The industry has a similar value range of 48% to 54%. The ear size average was 21.57 cm, row number was 15, ear diameter 45.54 mm and the kernel corn deep was 8.57 mm. All these measurements were found not different from commercial values found for the industry. All corn samples evaluated showed good stability despites the frozen processing and storage. Hybrid 2038 ranked higher in quality.

  11. Distortion product otoacoustic emissions upon ear canal pressurization.

    PubMed

    Zebian, Makram; Schirkonyer, Volker; Hensel, Johannes; Vollbort, Sven; Fedtke, Thomas; Janssen, Thomas

    2013-04-01

    The purpose of this study was to quantify the change in distortion product otoacoustic emission (DPOAE) level upon ear canal pressurization. DPOAEs were measured on 12 normal-hearing human subjects for ear canal static pressures between -200 and +200 daPa in (50 ± 5) daPa steps. A clear dependence of DPOAE levels on the pressure was observed, with levels being highest at the maximum compliance of the middle ear, and decreasing on average by 2.3 dB per 50 daPa for lower and higher pressures. Ear canal pressurization can serve as a tool for improving the detectability of DPOAEs in the case of middle-ear dysfunction.

  12. Cilia and Ear.

    PubMed

    Piatti, Gioia; De Santi, Maria Margherita; Torretta, Sara; Pignataro, Lorenzo; Soi, Daniela; Ambrosetti, Umberto

    2017-04-01

    To investigate the prevalence of otological complications derived from primary ciliary dyskinesia (PCD) in adulthood. Twenty-three patients with diagnosed PCD underwent medical history aimed at recording the presence of ear, nose, and throat manifestations (ENT) and any surgical treatments. The ENT objectivity was annotated, and then patients were subjected to audiometric test, tympanometry, registration of otoacoustic emission, and vestibular evaluation. Otitis media with chronic middle ear effusion (OME) during childhood was reported in 52% of the subjects, no patient had undergone ear surgery, and only 2 patients had an episode of otitis in the last year. Eleven of 23 patients showed normal hearing, 11 had a conductive hearing impairment, and 1 showed a severe sensorineural hearing loss unrelated to the syndrome. The bilateral stapedial reflex was only found in all cases of normoacusia and type A tympanogram, distortion product otoacoustic emissions (DPOAE) were present in 8 patients, and no patient had vestibular alterations. Our study confirms a very frequent prevalence of OME in PCD during childhood. Careful monitoring of otological complications of the syndrome is always desirable, also given the high presence in adults of other manifestations in the upper airways, such as chronic rhinosinusitis and nasal polyposis.

  13. Why Internally Coupled Ears (ICE) Work Well

    NASA Astrophysics Data System (ADS)

    van Hemmen, J. Leo

    2014-03-01

    Many vertebrates, such as frogs and lizards, have an air-filled cavity between left and right eardrum, i.e., internally coupled ears (ICE). Depending on source direction, internal time (iTD) and level (iLD) difference as experienced by the animal's auditory system may greatly exceed [C. Vossen et al., JASA 128 (2010) 909-918] the external, or interaural, time and level difference (ITD and ILD). Sensory processing only encodes iTD and iLD. We present an extension of ICE theory so as to elucidate the underlying physics. First, the membrane properties of the eardrum explain why for low frequencies iTD dominates whereas iLD does so for higher frequencies. Second, the plateau of iTD = γ ITD for constant 1 < γ < 5 and variable input frequency <ν∘ follows; e.g., for the Tockay gecko ν∘ ~ 1 . 5 kHz. Third, we use a sectorial instead of circular membrane to quantify the effect of the extracolumella embedded in the tympanum and connecting with the cochlea. The main parameters can be adjusted so that the model is species independent. Work done in collaboration with A.P. Vedurmudi and J. Goulet; partially supported by BCCN-Munich.

  14. Inner Ear Gene Transfection in Neonatal Mice Using Adeno-Associated Viral Vector: A Comparison of Two Approaches

    PubMed Central

    Xia, Li; Yin, Shankai; Wang, Jian

    2012-01-01

    Local gene transfection is a promising technique for the prevention and/or correction of inner ear diseases, particularly those resulting from genetic defects. Adeno-associated virus (AAV) is an ideal viral vector for inner ear gene transfection because of its safety, stability, long-lasting expression, and its high tropism for many different cell types. Recently, a new generation of AAV vectors with a tyrosine mutation (mut-AAV) has demonstrated significant improvement in transfection efficiency. A method for inner ear gene transfection via the intact round window membrane (RWM) has been developed in our laboratory. This method has not been tested in neonatal mice, an important species for the study of inherited hearing loss. Following a preliminary study to optimize the experimental protocol in order to reduce mortality, the present study investigated inner ear gene transfection in mice at postnatal day 7. We compared transfection efficiency, the safety of the scala tympani injection via RWM puncture, and the trans-RWM diffusion following partial digestion with an enzyme technique. The results revealed that approximately 47% of inner hair cells (IHCs) and 17% of outer hair cells (OHCs) were transfected via the trans-RWM approach. Transfection efficiency via RWM puncture (58% and 19% for IHCs and OHCs, respectively) was slightly higher, but the difference was not significant. PMID:22912830

  15. Usher proteins in inner ear structure and function.

    PubMed

    Ahmed, Zubair M; Frolenkov, Gregory I; Riazuddin, Saima

    2013-11-01

    Usher syndrome (USH) is a neurosensory disorder affecting both hearing and vision in humans. Linkage studies of families of USH patients, studies in animals, and characterization of purified proteins have provided insight into the molecular mechanisms of hearing. To date, 11 USH proteins have been identified, and evidence suggests that all of them are crucial for the function of the mechanosensory cells of the inner ear, the hair cells. Most USH proteins are localized to the stereocilia of the hair cells, where mechano-electrical transduction (MET) of sound-induced vibrations occurs. Therefore, elucidation of the functions of USH proteins in the stereocilia is a prerequisite to understanding the exact mechanisms of MET.

  16. Sheep as a large animal ear model: Middle-ear ossicular velocities and intracochlear sound pressure.

    PubMed

    Péus, Dominik; Dobrev, Ivo; Prochazka, Lukas; Thoele, Konrad; Dalbert, Adrian; Boss, Andreas; Newcomb, Nicolas; Probst, Rudolf; Röösli, Christof; Sim, Jae Hoon; Huber, Alexander; Pfiffner, Flurin

    2017-08-01

    Animals are frequently used for the development and testing of new hearing devices. Dimensions of the middle ear and cochlea differ significantly between humans and commonly used animals, such as rodents or cats. The sheep cochlea is anatomically more like the human cochlea in size and number of turns. This study investigated the middle-ear ossicular velocities and intracochlear sound pressure (ICSP) in sheep temporal bones, with the aim of characterizing the sheep as an experimental model for implantable hearing devices. Measurements were made on fresh sheep temporal bones. Velocity responses of the middle ear ossicles at the umbo, long process of the incus and stapes footplate were measured in the frequency range of 0.25-8 kHz using a laser Doppler vibrometer system. Results were normalized by the corresponding sound pressure level in the external ear canal (P EC ). Sequentially, ICSPs at the scala vestibuli and tympani were then recorded with custom MEMS-based hydrophones, while presenting identical acoustic stimuli. The sheep middle ear transmitted most effectively around 4.8 kHz, with a maximum stapes velocity of 0.2 mm/s/Pa. At the same frequency, the ICSP measurements in the scala vestibuli and tympani showed the maximum gain relative to the P EC (24 dB and 5 dB, respectively). The greatest pressure difference across the cochlear partition occurred between 4 and 6 kHz. A comparison between the results of this study and human reference data showed middle-ear resonance and best cochlear sensitivity at higher frequencies in sheep. In summary, sheep can be an appropriate large animal model for research and development of implantable hearing devices. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Predicting skin deficits through surface area measurements in ear reconstruction and adult ear surface area norms.

    PubMed

    Yazar, Memet; Sevim, Kamuran Zeynep; Irmak, Fatih; Yazar, Sevgi Kurt; Yeşilada, Ayşin Karasoy; Karşidağğ, Semra Hacikerim; Tatlidede, Hamit Soner

    2013-07-01

    Ear reconstruction is one of the most challenging procedures in plastic surgery practice. Many studies and techniques have been described in the literature for carving a well-pronounced framework. However, just as important as the cartilage framework is the ample amount of delicate skin coverage of the framework. In this report, we introduce an innovative method of measuring the skin surface area of the auricle from a three-dimensional template created from the healthy ear.The study group consisted of 60 adult Turkish individuals who were randomly selected (30 men and 30 women). The participant ages ranged from 18 to 45 years (mean, 31.5 years), and they had no history of trauma or congenital anomalies. The template is created by dividing the ear into aesthetic subunits and using ImageJ software to estimate the necessary amount of total skin surface area required.Reconstruction of the auricle is a complicated process that requires experience and patience to provide the auricular details. We believe this estimate will shorten the learning curve for residents and surgeons interested in ear reconstruction and will help surgeons obtain adequate skin to drape over the well-sculpted cartilage frameworks by providing a reference list of total ear skin surface area measurements for Turkish men and women.

  18. Assessment of PLGA-PEG-PLGA Copolymer Hydrogel for Sustained Drug Delivery in the Ear

    PubMed Central

    Feng, Liang; Ward, Jonette A.; Li, S. Kevin; Tolia, Gaurav; Hao, Jinsong; Choo, Daniel I.

    2014-01-01

    Temperature sensitive copolymer systems were previously studied using modified diffusion cells in vitro for intratympanic injection, and the PLGA-PEG-PLGA copolymer systems were found to provide sustained drug delivery for several days. The objectives of the present study were to assess the safety of PLGA-PEG-PLGA copolymers in intratympanic injection in guinea pigs in vivo and to determine the effects of additives glycerol and poloxamer in PLGA-PEG-PLGA upon drug release in the diffusion cells in vitro for sustained inner ear drug delivery. In the experiments, the safety of PLGA-PEG-PLGA copolymers to inner ear was evaluated using auditory brainstem response (ABR). The effects of the additives upon drug release from PLGA-PEG-PLGA hydrogel were investigated in the modified Franz diffusion cells in vitro with cidofovir as the model drug. The phase transition temperatures of the PLGA-PEG-PLGA copolymers in the presence of the additives were also determined. In the ABR safety study, the PLGA-PEG-PLGA copolymer alone did not affect hearing when delivered at 0.05-mL dose but caused hearing loss after 0.1-mL injection. In the drug release study, the incorporation of the bioadhesive additive, poloxamer, in the PLGA-PEG-PLGA formulations was found to decrease the rate of drug release whereas the increase in the concentration of the humectant additive, glycerol, provided the opposite effect. In summary, the PLGA-PEG-PLGA copolymer did not show toxicity to the inner ear at the 0.05-mL dose and could provide sustained release that could be controlled by using the additives for inner ear applications. PMID:24438444

  19. Middle ear infection (otitis media) (image)

    MedlinePlus

    Otitis media is an inflammation or infection of the middle ear. Acute otitis media (acute ear infection) occurs when there is ... which causes production of fluid or pus. Chronic otitis media occurs when the eustachian tube becomes blocked ...

  20. Cytotoxicity due to corrosion of ear piercing studs.

    PubMed

    Rogero, S O; Higa, O Z; Saiki, M; Correa, O V; Costa, I

    2000-12-01

    It is well known that allergic and/or inflammatory reactions can be elicited from the use of gold-coated studs, particularly the type used for piercing ears, since they are left in contact with body fluids until the puncture heals. Inasmuch as gold is known as a non-toxic element, other elements of the substrate material may be responsible for some allergies. Therefore, characteristics of the coating, such as defects that expose the substrate to the human skin or body fluids, play an important role in the development of skin sensitization. In this study, the cytotoxicity of commercial studs used for ear piercing and laboratory-made studs was determined in a culture of mammalian cells. The corrosion performance of the studs was investigated by means of weight loss measurements and electrochemical impedance spectroscopy. The elements that leached out into the medium were also analysed by instrumental neutron activation analysis. Further, the surfaces of the studs were examined by scanning electron microscopy and analysed by energy dispersive spectroscopy to identify defects and reaction products on the surface, both before and after their exposure to the culture medium. The stud which showed lower corrosion performance resulted in higher cytotoxicity. Ti showed no cytotoxicity and high corrosion resistance, proving to be a potential material for the manufacture of ear piercing studs.