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Balkan Medical Journal Sep 2017Morphologically congenital sensorineural hearing loss can be investigated under two categories. The majority of congenital hearing loss causes (80%) are membranous...
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.
Topics: Classification; Cochlea; Cochlear Nerve; Ear, Inner; Hearing Loss, Sensorineural; Humans; Osteogenesis; Temporal Bone; Tomography, X-Ray Computed
PubMed: 28840850
DOI: 10.4274/balkanmedj.2017.0367 -
Science Translational Medicine Mar 2019Permanent hearing loss affects more than 5% of the world's population, yet there are no nondevice therapies that can protect or restore hearing. Delivery of therapeutics... (Review)
Review
Permanent hearing loss affects more than 5% of the world's population, yet there are no nondevice therapies that can protect or restore hearing. Delivery of therapeutics to the cochlea and vestibular system of the inner ear is complicated by their inaccessible location. Drug delivery to the inner ear via the vasculature is an attractive noninvasive strategy, yet the blood-labyrinth barrier at the luminal surface of inner ear capillaries restricts entry of most blood-borne compounds into inner ear tissues. Here, we compare the blood-labyrinth barrier to the blood-brain barrier, discuss invasive intratympanic and intracochlear drug delivery methods, and evaluate noninvasive strategies for drug delivery to the inner ear.
Topics: Animals; Cochlea; Drug Delivery Systems; Ear, Inner; Hearing Loss; Humans; Permeability; Pharmaceutical Preparations
PubMed: 30842313
DOI: 10.1126/scitranslmed.aao0935 -
Nature Biotechnology Jun 2017The 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...
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.
Topics: Cells, Cultured; Ear, Inner; Hair Cells, Auditory, Inner; Humans; Organogenesis; Organoids; Pluripotent Stem Cells; Tissue Engineering
PubMed: 28459451
DOI: 10.1038/nbt.3840 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2021Maternal malnutrition during gestation and lactation is known to have adverse effects on offspring. We evaluate the impact of maternal diet on offspring bony labyrinth...
Maternal malnutrition during gestation and lactation is known to have adverse effects on offspring. We evaluate the impact of maternal diet on offspring bony labyrinth morphology. The bony labyrinth develops early and is thought to be stable to protect vital sensory organs within. For these reasons, bony labyrinth morphology has been used extensively to assess locomotion, hearing function, and phylogeny in primates and numerous other taxa. While variation related to these parameters has been documented, there is still a component of intraspecific variation that is unexplained. Although the labyrinthine developmental window is small, it may provide the opportunity for developmental instability to produce corresponding shape differences, as measured by fluctuating asymmetry (FA). We hypothesized that (a) offspring with poor maternal diet would exhibit increased FA, but (b) no unilateral shape difference. To test these hypotheses, we used two groups of rats (Rattus norvegicus; Crl:WI[Han] strain), one control group and one group exposed to a isocaloric, protein-restricted maternal diet during gestation and suckling. Individuals were sampled at weaning, sexual maturity, and old age. A Procrustes analysis of variance identified statistically significant FA in all diet-age subgroups. No differences in level of FA were identified among the subgroups, rejecting our first hypothesis. A principal components analysis identified no unilateral shape differences, supporting our second hypothesis. These results indicate that bony labyrinth morphology is remarkably stable and likely protected from a poor maternal diet during development. In light of this result, other factors must be explored to explain intraspecific variation in labyrinthine shape.
Topics: Animals; Ear, Inner; Female; Malnutrition; Maternal-Fetal Exchange; Pregnancy; Rats
PubMed: 33586866
DOI: 10.1002/ar.24601 -
Scientific Reports Jan 2019Carnivorans are a highly diverse and successful group of mammals, found on the top of the food chain. They originated in the Palaeocene (ca. 60 Ma) and have developed...
Carnivorans are a highly diverse and successful group of mammals, found on the top of the food chain. They originated in the Palaeocene (ca. 60 Ma) and have developed numerous lifestyles, locomotion modes and hunting strategies during their evolutionary history. Mechanosensory organs, such as the inner ear (which houses senses of equilibrium and hearing), represent informative anatomical systems to obtain insights into function, ecology and phylogeny of extant and extinct vertebrates. Using µCT scans, we examined bony labyrinths of a broad sample of various carnivoran species, to obtain new information about hunting behaviours of ancient carnivorans. Bony labyrinths were digitally reconstructed and measurements were taken directly from these 3D models. Principal component analyses generally separated various hunting strategies (pursuit, pounce, ambush and occasional), but also support their phylogenetic relationships (Canoidea vs. Feloidea). The height, width and length of all three semicircular canals show functional morphological adaptations, whereas the diameter of the canals, the height of the cochlea and particularly the angle between the lateral semicircular canal and the cochlea indicate a phylogenetic signal. The results demonstrate that the bony labyrinth provides a powerful ecological proxy reflecting both predatory habits as well as phylogenetic relationships in extinct and extant carnivorans.
Topics: Animals; Biometry; Carnivora; Ear, Inner; Fossils; Phylogeny; Predatory Behavior; X-Ray Microtomography
PubMed: 30635617
DOI: 10.1038/s41598-018-37106-4 -
Current Biology : CB Mar 2021Our understanding of the earliest evolution of jawed vertebrates depends on a credible phylogenetic framework for the jawed stem gnathostomes collectively known as...
Our understanding of the earliest evolution of jawed vertebrates depends on a credible phylogenetic framework for the jawed stem gnathostomes collectively known as "placoderms". However, their relationships, and whether placoderms represent a single radiation or a paraphyletic array, remain contentious. This uncertainty is compounded by an uneven understanding of anatomy across the group, particularly of the phylogenetically informative braincase and brain cavity-endocast. Based on new tomographic data, we here describe the endocast and bony labyrinth of Brindabellaspis stensioi from the Early Devonian of New South Wales. The taxon was commonly recovered as branching near the base of placoderms. Previous studies of Brindabellaspis emphasized its resemblances with fossil jawless fishes in the braincase anatomy and endocast proportions and its distinctive features were interpreted as autapomorphies, such as the elongated premedian region. Although our three-dimensional data confirmed the resemblance of its endocast to those of jawless vertebrates, we discovered that the inner ear and endolymphatic complex display a repertoire of previously unrecognized characters close to modern or crown-group jawed vertebrates, including a pronounced sinus superior and a vertical duct that connects the endolymphatic sac and the labyrinth cavity. Both parsimony and Bayesian analyses suggest that prevailing hypotheses of placoderm relationships are unstable, with newly revealed anatomy pointing to a radical revision of early gnathostome evolution. Our results call into question the appropriateness of arthrodire-like placoderms as models of primitive gnathostome anatomy and raise questions of homology relating to key cranial features.
Topics: Animals; Bayes Theorem; Biological Evolution; Ear, Inner; Fishes; Fossils; Phylogeny; Vertebrates
PubMed: 33508218
DOI: 10.1016/j.cub.2020.12.046 -
Physiological Research May 2018This review is focused on the unusual composition of the endolymph of the inner ear and its function in mechanoelectrical transduction. The role of K(+) and Ca(2+) in... (Review)
Review
This review is focused on the unusual composition of the endolymph of the inner ear and its function in mechanoelectrical transduction. The role of K(+) and Ca(2+) in excitatory influx, the very low Na(+), Ca(2+) and Mg(2+) concentrations of endolymph, stereocilia structure of hair cells and some proteins involved in mechanosensory signal transduction with emphasis on auditory receptors are presented and analyzed in more details. An alternative hypothetical model of ciliary structure and endolymph with a 'normal' composition is discussed. It is concluded that the unique endolymph cation content is more than an energy saving mechanism that avoids disturbing circulatory vibrations to achieve a much better mechanosensory resolution. It is the only possible way to fulfil the requirements for a precise ciliary mechanoelectrical transduction in conditions where pressure events with quite diverse amplitudes and duration are transformed into adequate hair cell membrane depolarizations, which are regulated by a sensitive Ca(2+)-dependent feedback tuning.
Topics: Animals; Ear, Inner; Endolymph; Hair Cells, Auditory, Inner; Humans; Mechanotransduction, Cellular
PubMed: 29303598
DOI: 10.33549/physiolres.933684 -
Anatomical Record (Hoboken, N.J. : 2007) Nov 2022Postmenopausal osteoporosis is a serious concern in aging individuals, but has not been explored for its potential to alter the shape of the inner ear by way of...
Postmenopausal osteoporosis is a serious concern in aging individuals, but has not been explored for its potential to alter the shape of the inner ear by way of increased remodeling in the otic capsule. The otic capsule, or bony labyrinth, is thought to experience uniquely limited remodeling after development due to high levels of osteoprotegerin. On this basis, despite the widespread remodeling that accompanies osteoporosis, we hypothesize that both the shape and volume of the semicircular canals will resist such changes. To test this hypothesis, we conducted three-dimensional geometric morphometric shape analysis on microcomputed tomographic data collected on the semicircular canals of an ovariectomized (OVX) rat model. A Procrustes ANOVA found no statistically significant differences in shape between surgery and sham groups, and morphological disparity testing likewise found no differences in shape variation. Univariate testing found no differences in semicircular volume between OVX and control groups. The range of variation in the OVX group, however, is greater than in the sham group but this difference does not reach statistical significance, perhaps because of a combination of small effect size and low sample size. This finding suggests that labyrinthine shape remains a tool for assessing phylogeny and function in the fossil record, but that it is possible that osteoporosis may be contributing to intraspecific shape variation in the bony labyrinth. This effect warrants further exploration at a microstructural level with continued focus on variables related to remodeling.
Topics: Animals; Rats; Fossils; Osteoporosis; Osteoprotegerin; Semicircular Canals; Ovariectomy; Female
PubMed: 35103405
DOI: 10.1002/ar.24878 -
Current Opinion in Neurobiology Aug 2008The 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... (Review)
Review
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.
Topics: Animals; Cell Differentiation; Cell Transdifferentiation; Ear, Inner; Hair Cells, Auditory; Humans; Regeneration; Stem Cell Transplantation; Stem Cells
PubMed: 18929656
DOI: 10.1016/j.conb.2008.10.001 -
Development (Cambridge, England) Jun 2023The inner ear sensory epithelia contain mechanosensitive hair cells and supporting cells. Both cell types arise from SOX2-expressing prosensory cells, but the mechanisms...
The inner ear sensory epithelia contain mechanosensitive hair cells and supporting cells. Both cell types arise from SOX2-expressing prosensory cells, but the mechanisms underlying the diversification of these cell lineages remain unclear. To determine the transcriptional trajectory of prosensory cells, we established a SOX2-2A-ntdTomato human embryonic stem cell line using CRISPR/Cas9, and performed single-cell RNA-sequencing analyses with SOX2-positive cells isolated from inner ear organoids at various time points between differentiation days 20 and 60. Our pseudotime analysis suggests that vestibular type II hair cells arise primarily from supporting cells, rather than bi-fated prosensory cells in organoids. Moreover, ion channel- and ion-transporter-related gene sets were enriched in supporting cells versus prosensory cells, whereas Wnt signaling-related gene sets were enriched in hair cells versus supporting cells. These findings provide valuable insights into how prosensory cells give rise to hair cells and supporting cells during human inner ear development, and may provide a clue to promote hair cell regeneration from resident supporting cells in individuals with hearing loss or balance disorders.
Topics: Humans; Organoids; Hair Cells, Auditory; Hair Cells, Vestibular; Vestibule, Labyrinth; Cell Differentiation
PubMed: 37381908
DOI: 10.1242/dev.201071