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Expert Opinion on Biological Therapy Feb 2019Sound is integral to communication and connects us to the world through speech and music. Cochlear hair cells are essential for converting sounds into neural impulses.... (Review)
Review
INTRODUCTION
Sound is integral to communication and connects us to the world through speech and music. Cochlear hair cells are essential for converting sounds into neural impulses. However, these cells are highly susceptible to damage from an array of factors, resulting in degeneration and ultimately irreversible hearing loss in humans. Since the discovery of hair cell regeneration in birds, there have been tremendous efforts to identify therapies that could promote hair cell regeneration in mammals.
AREAS COVERED
Here, we will review recent studies describing spontaneous hair cell regeneration and direct cellular reprograming as well as other factors that mediate mammalian hair cell regeneration.
EXPERT OPINION
Numerous combinatorial approaches have successfully reprogrammed non-sensory supporting cells to form hair cells, albeit with limited efficacy and maturation. Studies on epigenetic regulation and transcriptional network of hair cell progenitors may accelerate discovery of more promising reprogramming regimens.
Topics: Animals; Cellular Reprogramming; Ear, Inner; Epigenesis, Genetic; Hair Cells, Auditory; Humans; Regeneration
PubMed: 30584811
DOI: 10.1080/14712598.2019.1564035 -
Journal of Morphology Aug 2019The evolution of the various hearing adaptations is connected to major structural changes in nearly all groups of vertebrates. Besides hearing, the detection of... (Review)
Review
The evolution of the various hearing adaptations is connected to major structural changes in nearly all groups of vertebrates. Besides hearing, the detection of acceleration and orientation in space are key functions of this mechanosensory system. The symposium "show me your ear - the inner and middle ear in vertebrates" held at the 11th International Congress of Vertebrate Morphology (ICVM) 2016 in Washington, DC (USA) intended to present current research addressing adaptation and evolution of the vertebrate otic region, auditory ossicles, vestibular system, and hearing physiology. The symposium aimed at an audience with interest in hearing research focusing on morphological, functional, and comparative studies. The presented talks and posters lead to the contributions of this virtual issue highlighting recent advances in the vertebrate balance and hearing system. This article serves as an introduction to the virtual issue contributions and intends to give a short overview of research papers focusing on vertebrate labyrinth and middle ear related structures in past and recent years.
Topics: Animals; Ear, Inner; Ear, Middle; Hearing; Vertebrates
PubMed: 30117612
DOI: 10.1002/jmor.20880 -
Journal of Zhejiang University....Bone morphogenetic proteins (BMPs) are the largest subfamily of the transforming growth factor-β superfamily, and they play important roles in the development of... (Review)
Review
Bone morphogenetic proteins (BMPs) are the largest subfamily of the transforming growth factor-β superfamily, and they play important roles in the development of numerous organs, including the inner ear. The inner ear is a relatively small organ but has a highly complex structure and is involved in both hearing and balance. Here, we discuss BMPs and BMP signaling pathways and then focus on the role of BMP signal pathway regulation in the development of the inner ear and the implications this has for the treatment of human hearing loss and balance dysfunction.
Topics: Body Patterning; Bone Morphogenetic Protein Receptors; Bone Morphogenetic Proteins; Cell Differentiation; Cochlea; Ear, Inner; Hedgehog Proteins; Humans; Signal Transduction; Smad Proteins; Vestibule, Labyrinth; Wnt Signaling Pathway
PubMed: 30112880
DOI: 10.1631/jzus.B1800084 -
Nature Communications Oct 2022The labyrinth of the vertebrate inner ear is a sensory system that governs the perception of head rotations. Central hypotheses predict that labyrinth shape and size are...
The labyrinth of the vertebrate inner ear is a sensory system that governs the perception of head rotations. Central hypotheses predict that labyrinth shape and size are related to ecological adaptations, but this is under debate and has rarely been tested outside of mammals. We analyze the evolution of labyrinth morphology and its ecological drivers in living and fossil turtles, an understudied group that underwent multiple locomotory transitions during 230 million years of evolution. We show that turtles have unexpectedly large labyrinths that evolved during the origin of aquatic habits. Turtle labyrinths are relatively larger than those of mammals, and comparable to many birds, undermining the hypothesis that labyrinth size correlates directly with agility across vertebrates. We also find that labyrinth shape variation does not correlate with ecology in turtles, undermining the widespread expectation that reptilian labyrinth shapes convey behavioral signal, and demonstrating the importance of understudied groups, like turtles.
Topics: Animals; Birds; Ear, Inner; Fossils; Mammals; Phylogeny; Turtles
PubMed: 36220806
DOI: 10.1038/s41467-022-33091-5 -
Hearing Research Oct 2018The isolated anatomical position and blood-labyrinth barrier hampers systemic drug delivery to the mammalian inner ear. Intratympanic placement of drugs and permeation... (Review)
Review
The isolated anatomical position and blood-labyrinth barrier hampers systemic drug delivery to the mammalian inner ear. Intratympanic placement of drugs and permeation via the round- and oval window are established methods for local pharmaceutical treatment. Mechanisms of drug uptake and pathways for distribution within the inner ear are hard to predict. The complex microanatomy with fluid-filled spaces separated by tight- and leaky barriers compose various compartments that connect via active and passive transport mechanisms. Here we provide a review on the inner ear architecture at light- and electron microscopy level, relevant for drug delivery. Focus is laid on the human inner ear architecture. Some new data add information on the human inner ear fluid spaces generated with high resolution microcomputed tomography at 15 μm resolution. Perilymphatic spaces are connected with the central modiolus by active transport mechanisms of mesothelial cells that provide access to spiral ganglion neurons. Reports on leaky barriers between scala tympani and the so-called cortilymph compartment likely open the best path for hair cell targeting. The complex barrier system of tight junction proteins such as occludins, claudins and tricellulin isolates the endolymphatic space for most drugs. Comparison of relevant differences of barriers, target cells and cell types involved in drug spread between main animal models and humans shall provide some translational aspects for inner ear drug applications.
Topics: Animals; Drug Delivery Systems; Ear, Inner; Hearing; Hearing Loss; Humans; Labyrinth Diseases; Pharmaceutical Preparations
PubMed: 30442227
DOI: 10.1016/j.heares.2018.06.017 -
Anatomical Record (Hoboken, N.J. : 2007) May 2022The inner ear contains the end organs for balance (vestibular labyrinth) and hearing (cochlea). The vestibular labyrinth is comprised of the semicircular canals...
The inner ear contains the end organs for balance (vestibular labyrinth) and hearing (cochlea). The vestibular labyrinth is comprised of the semicircular canals (detecting angular acceleration) and otolith organs (utricle and saccule, which detect linear acceleration and head tilt relative to gravity). Lying just inferior to the utricle is the membranous membrana limitans (ML). Acting as a keystone to vestibular geometry, the ML provides support for the utricular macula and acts as a structural boundary between the superior (pars superior) and inferior (pars inferior) portions of the vestibular labyrinth. Given its importance in vestibular form, understanding ML morphology is valuable in establishing the spatial organization of other vestibular structures, particularly the utricular macula. Knowledge of the 3D structure and variation of the ML, however, remain elusive. Our study addresses this knowledge gap by visualizing, in 3D, the ML and surrounding structures using micro-CT data. By doing so, we attempt to clarify: (a) the variation of ML shape; (b) the reliability of ML attachment sites; and (c) the spatial relationship of the ML to the stapes footplate using landmark-based Generalized Procrustes, Principal Component and covariance analyses. Results indicate a consistent configuration of three distinct bony ML attachments including an anterolateral, medial, and posterior attachment which all covary with bony structure. Our results set the stage for further understanding into vestibular and more specifically, utricular macula spatial configuration within the human head, offering the potential to aid in clinical and evolutionary studies which rely on a 3D understanding of vestibular spatial configuration.
Topics: Biological Evolution; Humans; Imaging, Three-Dimensional; Reproducibility of Results; Semicircular Canals; Vestibule, Labyrinth
PubMed: 34021723
DOI: 10.1002/ar.24675 -
Journal of Anatomy Feb 2016The inner ear of mammals consists of the cochlea, which is involved with the sense of hearing, and the vestibule and three semicircular canals, which are involved with... (Review)
Review
The inner ear of mammals consists of the cochlea, which is involved with the sense of hearing, and the vestibule and three semicircular canals, which are involved with the sense of balance. Although different regions of the inner ear contribute to different functions, the bony chambers and membranous ducts are morphologically continuous. The gross anatomy of the cochlea that has been related to auditory physiologies includes overall size of the structure, including volume and total spiral length, development of internal cochlear structures, including the primary and secondary bony laminae, morphology of the spiral nerve ganglion, and the nature of cochlear coiling, including total number of turns completed by the cochlear canal and the relative diameters of the basal and apical turns. The overall sizes, shapes, and orientations of the semicircular canals are related to sensitivity to head rotations and possibly locomotor behaviors. Intraspecific variation, primarily in the shape and orientation of the semicircular canals, may provide additional clues to help us better understand form and function of the inner ear.
Topics: Animals; Ear, Inner; Hearing; Mammals
PubMed: 25911945
DOI: 10.1111/joa.12308 -
Seminars in Cell & Developmental Biology May 2017The vertebrate inner ear is a precision sensory organ, acting as both a microphone to receive sound and an accelerometer to detect gravity and motion. It consists of a... (Review)
Review
The vertebrate inner ear is a precision sensory organ, acting as both a microphone to receive sound and an accelerometer to detect gravity and motion. It consists of a series of interlinked, fluid-filled chambers containing patches of sensory epithelia, each with a specialised function. The ear contains many different differentiated cell types with distinct morphologies, from the flask-shaped hair cells found in thickened sensory epithelium, to the thin squamous cells that contribute to non-sensory structures, such as the semicircular canal ducts. Nearly all cell types of the inner ear, including the afferent neurons that innervate it, are derived from the otic placode, a region of cranial ectoderm that develops adjacent to the embryonic hindbrain. As the ear develops, the otic epithelia grow, fold, fuse and rearrange to form the complex three-dimensional shape of the membranous labyrinth. Much of our current understanding of the processes of inner ear morphogenesis comes from genetic and pharmacological manipulations of the developing ear in mouse, chicken and zebrafish embryos. These traditional approaches are now being supplemented with exciting new techniques-including force measurements and light-sheet microscopy-that are helping to elucidate the mechanisms that generate this intricate organ system.
Topics: Animals; Cell Differentiation; Cell Lineage; Cell Movement; Chick Embryo; Ectoderm; Epithelial Cells; Gene Expression Regulation, Developmental; Hair Cells, Auditory; Labyrinth Supporting Cells; Mice; Organogenesis; Species Specificity; Transcription Factors; Zebrafish
PubMed: 27686400
DOI: 10.1016/j.semcdb.2016.09.015 -
La Radiologia Medica Oct 2021In the multidisciplinary management of patients with inner ear malformations (IEMs), the correct diagnosis makes the differences in terms of clinical and surgical... (Review)
Review
In the multidisciplinary management of patients with inner ear malformations (IEMs), the correct diagnosis makes the differences in terms of clinical and surgical treatment. The complex anatomical landscape of the inner ear, comprising several small structures, makes imaging of this region particularly challenging for general radiologists. Imaging techniques are important for identifying the presence and defining the type of IEM and the cochlear nerve condition. High-resolution magnetic resonance imaging (MRI) sequences and high-resolution computed tomography (HRCT) are the mainstay imaging techniques in this area. Dedicated MRI and HRCT protocols play an important role in the diagnosis and treatment of patients with inner ear disease. The most suitable technique should be selected depending on the clinical setting. However, in cases of congenital malformation of the inner ear, these techniques should be considered complementary. Since prompt intervention has a positive impact on the treatment outcomes, early diagnosis of IEMs is very important in the management of deaf patients. This article reviews the key concepts of IEMs for clinical radiologists by focusing on recent literature updates, discusses the principal imaging findings and clinical implications for every IEM subgroup, thus providing a practical diagnostic approach.
Topics: Ear, Inner; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed
PubMed: 34196909
DOI: 10.1007/s11547-021-01387-z -
Hearing Research May 2018The environment of the inner ear is highly regulated in a manner that some solutes are permitted to enter while others are excluded or transported out. Drug therapies... (Review)
Review
The environment of the inner ear is highly regulated in a manner that some solutes are permitted to enter while others are excluded or transported out. Drug therapies targeting the sensory and supporting cells of the auditory and vestibular systems require the agent to gain entry to the fluid spaces of the inner ear, perilymph or endolymph, which surround the sensory organs. Access to the inner ear fluids from the vasculature is limited by the blood-labyrinth barriers, which include the blood-perilymph and blood-strial barriers. Intratympanic applications provide an alternative approach in which drugs are applied locally. Drug from the applied solution enters perilymph through the round window membrane, through the stapes, and under some circumstances, through thin bone in the otic capsule. The amount of drug applied to the middle ear is always substantially more than the amount entering perilymph. As a result, significant amounts of the applied drug can pass to the digestive system, to the vasculature, and to the brain. Drugs in perilymph pass to the vasculature and to cerebrospinal fluid via the cochlear aqueduct. Conversely, drugs applied to cerebrospinal fluid, including those given intrathecally, can enter perilymph through the cochlear aqueduct. Other possible routes in or out of the ear include passage by neuronal pathways, passage via endolymph and the endolymphatic sac, and possibly via lymphatic pathways. A better understanding of the pathways for drug movements in and out of the ear will enable better intervention strategies.
Topics: Animals; Drug Administration Routes; Drug Compounding; Ear, Inner; Humans; Perilymph; Permeability; Pharmaceutical Preparations; Tissue Distribution
PubMed: 29277248
DOI: 10.1016/j.heares.2017.12.010