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In Vivo (Athens, Greece) 2021Hearing loss is one of the major worldwide health problems that seriously affects human social and cognitive development. In the auditory system, three components outer... (Review)
Review
Hearing loss is one of the major worldwide health problems that seriously affects human social and cognitive development. In the auditory system, three components outer ear, middle ear and inner ear are essential for the hearing mechanism. In the inner ear, sensory hair cells and ganglion neuronal cells are the essential supporters for hearing mechanism. Damage to these cells can be caused by long-term exposure of excessive noise, ototoxic drugs (aminoglycosides), ear tumors, infections, heredity and aging. Since mammalian cochlear hair cells do not regenerate naturally, some therapeutic interventions may be required to replace the damaged or lost cells. Cochlear implants and hearing aids are the temporary solutions for people suffering from severe hearing loss. The current discoveries in gene therapy may provide a deeper understanding in essential genes for the inner ear regeneration. Stem cell migration, survival and differentiation to supporting cells, cochlear hair cells and spiral ganglion neurons are the important foundation in understanding stem cell therapy. Moreover, mesenchymal stem cells (MSCs) from different sources (bone marrow, umbilical cord, adipose tissue and placenta) could be used in inner ear therapy. Transplanted MSCs in the inner ear can recruit homing factors at the damaged sites to induce transdifferentiation into inner hair cells and ganglion neurons or regeneration of sensory hair cells, thus enhancing the cochlear function. This review summarizes the potential application of mesenchymal stem cells in hearing restoration and combining stem cell and molecular therapeutic strategies can also be used in the recovery of cochlear function.
Topics: Animals; Ear, Inner; Hair Cells, Auditory, Inner; Humans; Mesenchymal Stem Cells; Spiral Ganglion; Stem Cell Transplantation
PubMed: 33402445
DOI: 10.21873/invivo.12227 -
Journal of Anatomy May 2022Varanopids are a group of Palaeozoic terrestrial amniotes which represent one of the earliest-diverging groups of synapsids, but their palaeoneurology has gone largely...
Varanopids are a group of Palaeozoic terrestrial amniotes which represent one of the earliest-diverging groups of synapsids, but their palaeoneurology has gone largely unstudied and recent analyses have challenged their traditional placement within synapsids. We utilized computed tomography (CT) to study the virtual cranial and otic endocasts of six varanopids, including representative taxa of both mycterosaurines and varanodontines. Our results show that the varanopid brain is largely plesiomorphic, being tubular in shape and showing no expansion of the cerebrum or olfactory bulbs, but is distinct in showing highly expanded floccular fossae. The housing of the varanopid bony labyrinth is also distinct, in that the labyrinth is bounded almost entirely by the supraoccipital-opisthotic complex, with the prootic only bordering the ventral portion of the vestibule. The bony labyrinth is surprisingly well-ossified, clearly preserving the elliptical, sub-orthogonal canals, prominent ampullae, and the short, undifferentiated vestibule; this high degree of ossification is similar to that seen in therapsid synapsids and supports the traditional placement of varanopids within Synapsida. The enlarged anterior canal, together with the elliptical, orthogonal canals and enlarged floccular fossa, lend support for the fast head movements indicated by the inferred predatory feeding mode of varanopids. Reconstructed neurosensory anatomy indicates that varanopids may have a much lower-frequency hearing range compared to more derived synapsids, suggesting that, despite gaining some active predatory features, varanopids retain plesiomorphic hearing capabilities. As a whole, our data reveal that the neuroanatomy of pelycosaur-grade synapsids is far more complex than previously anticipated.
Topics: Biological Evolution; Ear, Inner; Fossils; Skull; Tomography, X-Ray Computed
PubMed: 34775594
DOI: 10.1111/joa.13593 -
LDL receptor-related protein 1 (LRP1), a novel target for opening the blood-labyrinth barrier (BLB).Signal Transduction and Targeted Therapy Jun 2022Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide. However, the presence of the blood-labyrinth barrier...
Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people worldwide. However, the presence of the blood-labyrinth barrier (BLB) on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability, which restricts the entry of most drug compounds from the bloodstream into the inner ear tissue. Here, we report the finding of a novel receptor, low-density lipoprotein receptor-related protein 1 (LRP1), that is expressed on the BLB, as a potential target for shuttling therapeutics across this barrier. As a proof-of-concept, we developed an LRP1-binding peptide, IETP2, and covalently conjugated a series of model small-molecule compounds to it, including potential drugs and imaging agents. All compounds were successfully delivered into the inner ear and inner ear lymph, indicating that targeting the receptor LRP1 is a promising strategy to enhance the permeability of the BLB. The discovery of the receptor LRP1 will illuminate developing strategies for crossing the BLB and for improving systemic drug delivery for inner ear disorders.
Topics: Drug Delivery Systems; Ear, Inner; Hearing Loss; Humans; Low Density Lipoprotein Receptor-Related Protein-1; Pharmaceutical Preparations
PubMed: 35680846
DOI: 10.1038/s41392-022-00995-z -
The International Journal of... 2017The inner ear is composed of a complex mixture of cells, which together allow organisms to hear and maintain balance. The cells in the inner ear, which undergo an... (Review)
Review
The inner ear is composed of a complex mixture of cells, which together allow organisms to hear and maintain balance. The cells in the inner ear, which undergo an extraordinary process of development, have only recently begun to be studied on an individual level. As it has recently become clear that individual cells, previously considered to be of uniform character, may differ dramatically from each other, the need to study cell-to-cell variation, along with distinct transcriptional and regulatory signatures, has taken hold in the scientific community. In conjunction with high-throughput technologies, attempts are underway to dissect the inter- and intra-cellular variability of different cell types and developmental states of the inner ear from a novel perspective. Single cell analysis of the inner ear sensory organs holds the promise of providing a significant boost in building an omics network that translates into a comprehensive understanding of the mechanisms of hearing and balance. These networks may uncover critical elements for trans-differentiation, regeneration and/or reprogramming, providing entry points for therapeutics of deafness and vestibular pathologies.
Topics: Animals; Cell Differentiation; Ear, Inner; Gene Expression Profiling; Gene Expression Regulation, Developmental; Genome; Humans; Microscopy, Fluorescence; Regeneration; Signal Transduction; Single-Cell Analysis; Stem Cells; Transcription, Genetic; Transcriptome
PubMed: 28621418
DOI: 10.1387/ijdb.160453ka -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Apr 2021As isolated anatomical position, limited labyrinthine artery supply, and blood-labyrinth barrier hampers systemic drug delivery to the inner ear. The efficient... (Review)
Review
As isolated anatomical position, limited labyrinthine artery supply, and blood-labyrinth barrier hampers systemic drug delivery to the inner ear. The efficient concentration of drug treatment is unsatisfactory and there's possible side effects after systemic administration. Intratympanic injection of drug can bypass the blood-labyrinth and permeated to the hair cells or synaptic area via the round-or oval window of the cochlea. Efficacy and safety of pharmacotherapy has become increasingly relied on the inner ear delivery carrier system. The goal of this review focus on the anatomical barrier that need to be overcome in the intratympanic applications, the improvement of drug retention and specific targets, and the safety of novel drug carriers, these emerging strategies of local drug delivery promise novel and better guidance for the clinical application.
Topics: Cochlea; Drug Carriers; Drug Delivery Systems; Ear, Inner; Round Window, Ear
PubMed: 33794643
DOI: 10.13201/j.issn.2096-7993.2021.04.022 -
Otology & Neurotology : Official... Jul 2022Automated image registration techniques can successfully determine anatomical variation in human temporal bones with statistical shape modeling.
HYPOTHESIS
Automated image registration techniques can successfully determine anatomical variation in human temporal bones with statistical shape modeling.
BACKGROUND
There is a lack of knowledge about inter-patient anatomical variation in the temporal bone. Statistical shape models (SSMs) provide a powerful method for quantifying variation of anatomical structures in medical images but are time-intensive to manually develop. This study presents SSMs of temporal bone anatomy using automated image-registration techniques.
METHODS
Fifty-three cone-beam temporal bone CTs were included for SSM generation. The malleus, incus, stapes, bony labyrinth, and facial nerve were automatically segmented using 3D Slicer and a template-based segmentation propagation technique. Segmentations were then used to construct SSMs using MATLAB. The first three principal components of each SSM were analyzed to describe shape variation.
RESULTS
Principal component analysis of middle and inner ear structures revealed novel modes of anatomical variation. The first three principal components for the malleus represented variability in manubrium length (mean: 4.47 mm; ±2-SDs: 4.03-5.03 mm) and rotation about its long axis (±2-SDs: -1.6° to 1.8° posteriorly). The facial nerve exhibits variability in first and second genu angles. The bony labyrinth varies in the angle between the posterior and superior canals (mean: 88.9°; ±2-SDs: 83.7°-95.7°) and cochlear orientation (±2-SDs: -4.0° to 3.0° anterolaterally).
CONCLUSIONS
SSMs of temporal bone anatomy can inform surgeons on clinically relevant inter-patient variability. Anatomical variation elucidated by these models can provide novel insight into function and pathophysiology. These models also allow further investigation of anatomical variation based on age, BMI, sex, and geographical location.
Topics: Ear, Inner; Humans; Imaging, Three-Dimensional; Incus; Malleus; Models, Statistical; Temporal Bone
PubMed: 35761465
DOI: 10.1097/MAO.0000000000003554 -
Journal of Anatomy Sep 2016Despite its growing use in anatomical and ecological studies, the morphological variability and ontogenetic development of the bony labyrinth have very rarely been...
Despite its growing use in anatomical and ecological studies, the morphological variability and ontogenetic development of the bony labyrinth have very rarely been investigated in ruminants. Here we study its morphology in 15 adult and 10 juvenile specimens in the three extant tragulid ruminant genera. Intraspecific and interspecific variability is quantified using morphometric and 3D geometric morphometrics analyses. The bony labyrinth of Tragulus, Hyemoschus, and Moschiola is strikingly different, clustering in clearly different morphospaces despite similar ecological adaptations. Although the bony labyrinths within two species of the same genus cannot be distinguished from each other based on the chosen semi-landmarks, discrete interspecific differences exist. We were able to show for the first time that an artiodactyl mammal in a late fetal stage possesses an almost fully formed bony labyrinth similar to that of adults. No significant change either occurs in size or morphology after ossification of the petrosal bone. Some intraspecific variation is observed on the shape of the lateral semi-circular canal, the size and shape of the common crus, the coil of the cochlea or the stapedial ratio. Variable structures are expected to be highly informative characters for a large cladistic analysis. They can be used for phylogenetic studies in ruminants. Incorporating juvenile specimens in studies is not problematic, as they fall within the morphological range of adults.
Topics: Animals; Biological Evolution; Ear, Inner; Female; Imaging, Three-Dimensional; Male; Phylogeny; Ruminants; Species Specificity
PubMed: 27245372
DOI: 10.1111/joa.12487 -
The FEBS Journal Dec 2022The inner ear is a complex organ that encodes sound, motion, and orientation in space. Given the complexity of the inner ear, it is not surprising that treatments are... (Review)
Review
The inner ear is a complex organ that encodes sound, motion, and orientation in space. Given the complexity of the inner ear, it is not surprising that treatments are relatively limited despite the fact that, in 2015, hearing loss was the fourth leading cause of years lived with disability worldwide. Inner ear organoid models are a promising tool to advance the study of multiple aspects of the inner ear to aid the development of new treatments and validate drug-based therapies. The blood supply of the inner ear plays a pivotal role in growth, maturation, and survival of inner ear tissues and their physiological functions. This vasculature cannot be ignored in order to achieve a truly in vivo-like model that mimics the microenvironment and niches of organ development. However, this aspect of organoid development has remained largely absent in the generation of inner ear organoids. The current review focuses on three-dimensional inner ear organoid and how recent technical progress in generating in vitro vasculature can enhance the next generation of these models.
Topics: Ear, Inner
PubMed: 34331740
DOI: 10.1111/febs.16146 -
Anatomical Record (Hoboken, N.J. : 2007) Apr 2018The inner ear is a very complicated structure, composed of a bony labyrinth (otic capsule; OC), membranous labyrinth, with a space between them, named the periotic...
The inner ear is a very complicated structure, composed of a bony labyrinth (otic capsule; OC), membranous labyrinth, with a space between them, named the periotic labyrinth or periotic space. We investigated how periotic tissue fluid spaces covered the membranous labyrinth three-dimensionally, leading to formation of the periotic labyrinth encapsulated in the OC during human fetal development. Digital data sets from magnetic resonance images and phase-contrast X-ray tomography images of 24 inner ear organs from 24 human fetuses from the Kyoto Collection (fetuses in trimesters 1 and 2; crown-rump length: 14.4-197 mm) were analyzed. The membranous labyrinth was morphologically differentiated in samples at the end of the embryonic period (Carnegie stage 23), and had grown linearly to more than eight times in size during the observation period. The periotic space was first detected at the 35-mm samples, around the vestibule and basal turn of the cochlea, which elongated rapidly to the tip of the cochlea and semicircular ducts, successively, and almost covered the membranous labyrinth at the 115-mm CRL stage or later. In those samples, several ossification centers were detected around the space. This article thus demonstrated that formation of the membranous labyrinth, periotic space (labyrinth), and ossification of the OC occurs successively, according to an intricate timetable. Anat Rec, 301:563-570, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Ear, Inner; Female; Fetal Development; Humans; Magnetic Resonance Imaging; Organogenesis; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Tomography, X-Ray Computed; Ultrasonography, Prenatal; Vestibule, Labyrinth
PubMed: 29293291
DOI: 10.1002/ar.23764 -
Asian Journal of Surgery Dec 2023Teachers have applied the "Hand as Foot" teaching method in anatomy teaching. It helps students understand and remember effectively, triggers students' interest in...
Teachers have applied the "Hand as Foot" teaching method in anatomy teaching. It helps students understand and remember effectively, triggers students' interest in learning, and stimulates creativity. Guided by the teacher, my classmates and I also attempted to design some simple gestures to show the anatomical structures of the bony labyrinth to facilitate memorization. Here, as a medical student, I am glad to share my ideas with you.
Topics: Humans; Learning; Hand; Students, Medical; Foot; Ear, Inner
PubMed: 37537071
DOI: 10.1016/j.asjsur.2023.07.135