Inner Ear Tissues Research Articles

A Digitally-Controlled Integrated Circuit Solution for Tinnitus Treatment with Charge Balancing.

An integrated circuit specified for tinnitus treatment is described. This chip, realized using a 0.18um BCD high-voltage CMOS process, is capable of generating current stimulus with any wave shape directly into the inner-ear tissue without the need for off-chip control circuitry. Used as part of a multi-chip module that can be implanted into the inner ear, this core chip contains an 8-bit digital-to-analog converter, an amplitude control block, a novel high-voltage drive and charge balance circuit, a high-voltage level shifter, an SRAM, a ROM, and an on-chip central control unit. The chip can achieve ±0.1 mV charge-balance precision.

Super-resolution segmentation network for inner-ear tissue segmentation.

Cochlear implants (CIs) are considered the standard-of-care treatment for profound sensory-based hearing loss. Several groups have proposed computational models of the cochlea in order to study the neural activation patterns in response to CI stimulation. However, most of the current implementations either rely on high-resolution histological images that cannot be customized for CI users or CT images that lack the spatial resolution to show cochlear structures. In this work, we propose to use a deep learning-based method to obtain μCT level tissue labels using patient CT images. Experiments showed that the proposed super-resolution segmentation architecture achieved very good performance on the inner-ear tissue segmentation. Our best-performing model (0.871) outperformed the UNet (0.746), VNet (0.853), nnUNet (0.861), TransUNet (0.848), and SRGAN (0.780) in terms of mean dice score.

Intratympanic Steroid Treatments May Improve Hearing via Ion Homeostasis Alterations and Not Immune Suppression.

The inner ear (IE) endothelium is capable of responding to therapeutic steroids by altering the local expression of cytokine and ion homeostasis genes that impact inflammation and fluid regulation. Glucocorticoids are often given transtympanically for hearing disorders because of their anti-inflammatory effects, but their direct impact on IE ion homeostasis and cytokine gene expression has not been studied. The middle ears of Balb/c mice were transtympanically injected with 5 μL of phosphate-buffered saline, prednisolone (Pred), or dexamethasone (Dex). Untreated mice were used as controls. Mice were euthanized at 6, 24, and 72 hours; the cochleas were harvested; and total RNA was isolated from the IE tissues. Expression of eight cytokine genes and 24 ion homeostasis genes was analyzed with quantitative real time reverse transcription polymerase chain reaction. Phosphate-buffered saline caused upregulation of inflammatory cytokine genes that peaked at 6 hours. Surprisingly, Pred and Dex also caused upregulation of most cytokine genes. Interestingly, ion homeostasis genes were predominantly upregulated with Dex and Pred, with Pred having a larger effect. In the murine model, intratympanic steroids caused an initial upregulation of inflammatory cytokine genes in the IE, as well as predominant upregulation of ion homeostasis genes. These findings suggest that glucocorticoids do not suppress IE inflammation but rather cause an initial inflammatory response in the IE. Thus, inflammatory gene suppression is not a likely mechanism for their hearing restorative effects. On the other hand, these steroids have a significant mineralocorticoid function, as demonstrated by increased function of ion homeostasis genes, implicating their ionic and fluid regulatory properties as a mechanism for their therapeutic effects.

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

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.

Functional Mutation of SMAC/DIABLO, Encoding a Mitochondrial Proapoptotic Protein, Causes Human Progressive Hearing Loss DFNA64

SMAC/DIABLO is a mitochondrial proapoptotic protein that is released from mitochondria during apoptosis and counters the inhibitory activities of inhibitor of apoptosis proteins, IAPs. By linkage analysis and candidate screening, we identified a heterozygous SMAC/DIABLO mutation, c.377C>T (p.Ser126Leu, refers to p.Ser71Leu in the mature protein) in a six-generation Chinese kindred characterized by dominant progressive nonsyndromic hearing loss, designated as DFNA64. SMAC/DIABLO is highly expressed in human embryonic ears and is enriched in the developing mouse inner-ear hair cells, suggesting it has a role in the development and homeostasis of hair cells. We used a functional study to demonstrate that the SMAC/DIABLO(S71L) mutant, while retaining the proapoptotic function, triggers significant degradation of both wild-type and mutant SMAC/DIABLO and renders host mitochondria susceptible to calcium-induced loss of the membrane potential. Our work identifies DFNA64 as the human genetic disorder associated with SMAC/DIABLO malfunction and suggests that mutant SMAC/DIABLO(S71L) might cause mitochondrial dysfunction.

Anatomy of the human cochlea – implications for cochlear implantation

Since the classical description by Retzius in 1884, many extensive studies of the micro-anatomy of the human cochlea have been presented. The human cochlea is one of the most difficult tissues to study due to the bony capsule and its delicate contents. Most preparations suffer from post-mortem changes caused by the delay between demise and fixation. For over a decade, we have analyzed human inner-ear tissue obtained at surgery using transmission electron microscopy, scanning electron microscopy, in vitro culture, and immunohistochemistry. These studies show the value of these techniques for fine structural and molecular analyses. Modern cochlear implant surgery requires that ear surgeons are familiar with the intricate anatomy of the human cochlea and its variations. The classical technique to insert electrode arrays through a drilled cochleostomy has been abandoned by some surgeons today. Instead a round-window approach can be used as originally implemented by William House for short electrodes. This so-called ‘hook’ region of the cochlea presents extensive anatomical variations that can be difficult to foresee on pre-operative computed tomography. CI depends on the functional status of remaining spiral ganglion neurons. These cells are more or less preserved in CI patients but how the conservation influences the outcome of CI is debatable. Notwithstanding their preservation is crucial and more information should be attained about their deterioration and how it can be prevented. Better understanding of structure, function, and regenerative capability is needed to comprehend the nature of electrical stimulation of the peripheral and central nervous system to improve the design of future implant systems.

Research Symposium Probes Neural Regeneration

You have accessThe ASHA LeaderASHA News1 Jan 2010Research Symposium Probes Neural Regeneration Margaret RogersPhD, CCC-SLP Margaret Rogers Google Scholar More articles by this author , PhD, CCC-SLP https://doi.org/10.1044/leader.AN4.15012010.26 SectionsAbout ToolsAdd to favorites ShareFacebookTwitterLinked In More than 100 scientists and clinical professionals gathered in New Orleans in November for “Neural Regeneration and Communication Processes,” ASHA’s 19th annual research symposium. The full-day symposium, held concurrently with the annual ASHA convention, is funded by the National Institute on Deafness and Other Communication Disorders (NIDCD). The event is organized by ASHA’s Scientific Informatics and Research Programs unit and supported by ASHA members who wrote the grant application in 2006 that funds the symposia through 2011. This year’s symposium, organized by Julie Barkmeier-Kraemer (University of Arizona) and Brenda Ryalls (James Madison University), featured three renowned senior scientists: Tessa Gordon (University of Alberta), who spoke on the physiology of neural injury and regeneration in both the central nervous system and the peripheral nervous system; Jeff Kleim (University of Florida), who addressed neural regeneration of the motor cortex, especially as it relates to rehabilitation; and Yehoash Raphael (University of Michigan Medical School) who discussed inner-ear tissue engineering to restore hearing. The symposium also features the work of more junior scientists; the 2009 presenters and topics included Kazuo Oshima (Stanford University), hair cell regeneration through manipulation of stem cells; Michele Ciucci (University of Wisconsin-Madison), striatal-dopaminergic neuron recovery with behavioral intervention; and Doug Van Daele (University of Iowa), laryngeal muscle fiber changes with denervation. ASHA’s annual research symposium grants fund convention and symposium attendance for up to five doctoral students and provides a structure for these individuals to be mentored throughout convention. The 2009 recipients of the Research Symposium Mentoring-Pair award were: Yi-Chi Lo (University of Wisconsin-Madison) and mentor Cynthia Fowler (University of Wisconsin-Madison); Stacy Harnish (University of Florida) and mentor Jeff Kleim (University of Florida); Jun Wang (University of Nebraska-Lincoln) and mentor Brad Story (University of Arizona); Michelle Quinn (University of Iowa) and mentor Bruce Tomblin (University of Iowa); and Peter Meulenbroek (University of Wisconsin-Madison) and mentor Malcolm McNeil (University of Pittsburgh). The mentors and mentees also were invited to participate in a luncheon that featured Steve Barlow (University of Kansas) and Diane Bless (University of Wisconsin-Madison), who spoke about the importance and challenges of developing and maintaining research collaborations. Future research symposia topics include: Neural Plasticity: Mechanisms and Drivers of Functional Recovery in the Mature Brain (2010 ASHA convention) will examine the different forms and theories of neural plasticity and how the factors driving brain plasticity may be applied to the rehabilitation of individuals with acquired neurological communication and swallowing disorders. Neurobiological Bases of Auditory and Speech Perception (2011 ASHA convention). Research Symposia Planning Committee ASHA volunteers involved in writing the NIDCD grant and planning the 2007–2011 research symposia include: Julie Barkmeier-Kraemer, University of Arizona Steven Barlow, University of Kansas Marc Fey, University of Kansas Medical Center Lisa Hunter, University of Utah-Health Science Center Amanda Owen, University of Iowa Leslie Gonzalez Rothi, University of Florida/VAMC Margaret Rogers, ASHA (then at the University of Washington) Brenda Ryals, James Madison University Diane Scott, North Carolina Central University Linda Shuster, West Virginia University Author Notes Margaret Rogers, PhD, CCC-SLP, chief staff officer for science and research, can be reached at [email protected] for information on the symposia or other research initiatives. Additional Resources FiguresSourcesRelatedDetails Volume 15Issue 1January 2010 Get Permissions Add to your Mendeley library History Published in print: Jan 1, 2010 Metrics Downloaded 131 times Topicsasha-topicsleader_do_tagleader-topicsasha-article-typesCopyright & Permissions© 2010 American Speech-Language-Hearing AssociationLoading ...

Sensorineural hearing impairment resulted from radiochemotherapy in patients with nasopharyngeal carcinom

Objective To compare the severity of sensorineural hearing impairment resulted from radiotherapy (RT) and radiochemotberapy (CRT) in patients with nasopharyngeal carcinoma (NPC). Methods Between March 2002 and May 2007, 100 initially diagnosed NPC patients in Shandong Tumor Hospital and Qi Lu Hospital were randomized to RT group and CRT group. All patients underwent intensity modulated radiation therapy. In CRT group, concurrent and adjuvant CDDP were administered (CDDP 25 mg/m~2/d for 3 days to 4 cycles). Pure tone auditory threshold examination was performed 1 week ,6 months, 1 year and 2 years after the completion of radiotherapy. Statistical analyses were performed using Mann-Whit-ney U test,chi-square test and Fisber's exact probability test. Results The high-frequency threshold was significantly increased in CRT group comparing with RT group at 1- and 2-year after the treatment. In RT group, the hearing threshold was impaired immediately after the treatment, partially recovered within the first year but impaired again after 2 years. In CRT group, hearing threshold was impaired at the same time and kept getting worse until 1 year after radiotherapy, which could not be recovered. Conclusions Patients with NPC treated with radiotherapy and concurrent/adjuvant chemotherapy have more severe sensorineural hearing impairment comparing with those with radiotherapy alone, especially to the high frequency sound in the speech range. Inner ear tissue tolerance should be redefined for patients receiving radiochemotherapy. Key words: Nasopharyngeal neoplasms/radiotherapy; Intensity modulated; Nasopharyngeal neo-plasms/radioehemotherapy; Hearing impaired; sensorineural

Analysis and functional evaluation of the hair-cell transcriptome

An understanding of the molecular bases of the morphogenesis, organization, and functioning of hair cells requires that the genes expressed in these cells be identified and their functions ascertained. After purifying zebrafish hair cells and detecting mRNAs with oligonucleotide microarrays, we developed a subtractive strategy that identified 1,037 hair cell-expressed genes whose cognate proteins subserve functions including membrane transport, synaptic transmission, transcriptional control, cellular adhesion and signal transduction, and cytoskeletal organization. To assess the validity of the subtracted hair-cell data set, we verified the presence of 11 transcripts in inner-ear tissue. Functional evaluation of two genes from the subtracted data set revealed their importance in hair bundles: zebrafish larvae bearing the seahorse and ift 172 mutations display specific kinociliary defects. Moreover, a search for candidate genes that underlie heritable deafness identified a human ortholog of a zebrafish hair-cell gene whose map location is bracketed by the markers of a deafness locus.

A reevaluation of empiric therapy for peritoneal dialysis-related peritonitis

A reevaluation of empiric therapy for peritoneal dialysis-related peritonitis

Construction and characterization of a vestibular-specific cDNA library using T7-based RNA amplification.

Using a very small amount of inner-ear tissue, we constructed a human vestibular cDNA library by means of T7-based amplification of RNA. This library should allow us to identify genes likely to be involved in auditory and vestibular functions. Here we first report the characterization of the human vestibular cDNA library. Among 506 cDNA clones randomly selected from the vestibular cDNA library, DNA sequences of 301 cDNA clones were identical to those of genes of known function. Twenty-two cDNA clones were considered to be novel because they did not match any cDNA sequences in the public database. The information in our study will provide a valuable resource for identifying several novel genes underlying deafness disorders and vestibular dysfunction.

Identification of CRYM as a Candidate Responsible for Nonsyndromic Deafness, through cDNA Microarray Analysis of Human Cochlear and Vestibular Tissues

Through cDNA microarray analysis of gene expression in human cochlea and vestibule, we detected strong expression of mu-crystallin (CRYM; also known as "NADP-regulated thyroid hormone-binding protein") only in these inner-ear tissues. In a subsequent search for mutations of CRYM, among 192 patients with nonsyndromic deafness, we identified two mutations at the C-terminus; one was a de novo change (X315Y) in a patient with unaffected parents, and the other was a missense mutation (K314T) that segregated dominantly in the proband's family. When the mutated proteins were expressed in COS-7 cells, their subcellular localizations were different from that of the normal protein: the X315Y mutant showed vacuolated distribution in the cytoplasm, and the K314T mutant localized in perinuclear areas, whereas normal protein was distributed homogeneously in the cytoplasm. Aberrant intracellular localization of the mutated proteins might cause dysfunction of the CRYM product and result in hearing impairment. In situ hybridization analysis using mouse tissues indicated its expression in the lateral region of the spiral ligament and the fibrocytes of the spiral limbus, implying its possible involvement in the potassium-ion recycling system. Our results strongly implicate CRYM in normal auditory function and identify it as one of the genes that can be responsible for nonsyndromic deafness.

Molecular Cloning and Mapping of the Human Nicotinic Acetylcholine Receptor α10 (CHRNA10)

We report the isolation and initial characterization of a new member of the human nicotinic acetylcholine receptor (nAChR) subunit family, α10 (CHRNA10), from both inner-ear neuroepithelium and lymphoid tissue. The cDNA is 1959 nucleotides in length, with a coding region predicting a protein of 451 amino acids that is 90% identical to rat α10. The α10 gene was localized to chromosome 11p15.5. Human α10 was detected in human inner-ear tissue, tonsil, immortalized B-cells, cultured T-cells and peripheral blood lymphocytes using reverse transcriptase-polymerase chain reaction, Northern blot hybridization, and immunohistochemistry. We also detected the expression of the human nAChR α9 (CHRNA9) mRNA in these same tissues using RT-PCR and Northern blot hybridization.

Human autoantibodies and monoclonal antibody KHRI-3 bind to a phylogenetically conserved inner-ear-supporting cell antigen.

Autoimmunity is thought to be one cause of sensorineural hearing loss (SNHL). Sera from patients with rapidly progressive hearing loss have been shown to contain antibodies to a 68-kD protein in heterologous inner-ear tissue. Using guinea pig inner-ear tissue as the antigenic substrate and either Western blot or immunofluorescence (IF) or both, we tested sera from 74 patients suspected to have autoimmune hearing loss for inner-ear antibodies. Sera from 73 patients were tested by Western blot, and sera from 36 were tested by IF. Thirty-seven of 73 (51%) had antibody to a 68-70-kD protein by Western blot. Sera positive by IF stained supporting cells with a staining pattern like that previously observed with the KHRI-3 monoclonal antibody. There was concordance between Western blot and IF assays. Of 36 patients tested by both assays, 29/31 (94%) that were positive in Western blot were also positive by IF, three were negative by both tests, and two each were positive by one assay but negative by the other. Absorption of patient sera with human inner-ear tissue removed antibody reactivity to the guinea pig supporting cells, indicating that the antigen detected by the autoantibody is also present in the human inner ear. Absorption with an equal volume of white or red blood cells from the tissue donor did not remove the antibody reactivity to inner ear, showing that the absorption by inner-ear tissue is specific. Sera from three patients positive in both assays also stained a 68-70-kD inner-ear protein immunoprecipitated by the KHRI-3 monoclonal antibody, indicating that the monoclonal and human antibodies recognize the same antigen. The results support the hypothesis that patients with autoimmune sensorineural hearing loss produce autoantibodies to an inner-ear supporting cell antigen that is phylogenetically conserved and defined by the murine monoclonal antibody KHRI-3. Since KHRI-3 can induce hearing loss after infusion into the inner ear, it is likely that autoantibodies with the same antigenic target are also pathogenic in humans.

Induction of an inner-ear-specific autoreactive T-cell line for the diagnostic evaluation of an autoimmune disease of the inner ear.

Different patterns of sensorineural hearing loss with a potential improvement in auditory function following immunosuppressive therapy might be caused by an isolated autoimmune disease of the inner ear. Because of the lack of well-defined detection methods to identify autoimmune processes within the inner ear and the fact that the human inner ear is one of the few organs of the body not amenable to diagnostic biopsy, there has been great interest in developing animal models. Previous studies found evidence that this entity might be cellular mediated. By heterologeous immunization of inbred Lewis rats with inner-ear tissue, an autoreactive inner-ear-specific T-cell line was established. After passive transfer of these cells, a labyrinthitis was induced in recipient animals. The experimental design can serve as an animal model for a cellular-mediated autoimmune disease of the inner ear. Further studies have to split the cochlear proteins and to identify the protein with the strongest autoimmunological potency. After biotechnical production of this protein, a clinical test to diagnose an autoimmune disease of the inner ear in man should be possible.

Ménière's disease and autoimmunity.

Identifying the etiopathogenesis of MtniBre’s disease (MD) has been the object of several studies since Prosper MCnikre first described the main symptoms of this disease in 1861 : fluctuating hearing loss, vertigo, and tinnitus. Endolymphatic hydrops is considered the main pathological finding associated with MD and a good deal of research has been directed toward the identification and understanding of its underlying mechanisms. Because the sensory neural elements of the inner ear cannot be visualized in their diseased state in vivo, diagnosis of MD has been based mainly on the evaluation of the clinical symptoms and results of audiological tests. Since Rask-Andersen and Stahle’ first recognized the inner ear as having an immunological function, several authors have added their support to the idea of a multifactorial origin by hypothesizing a possible role of the immunological system in MD pathogenesis. In fact, in 1983 Shea described the possible role of autoimmune mechanisms in patients with typical MD who responded favorably to steroid treatment or plasmapheresis.* Immunohistochemical studies also revealed the presence of an immunological reaction within the inner-ear tissues, such as stria vascularis, supporting connective tissues and blood vessels, in only a small number of patients inve~tigated.~-~ Although these studies are certainly affected by technical problems mainly linked to tissue preservation and processing, they are still suggestive of the idea that certain types of MD are caused by immunological factors of the inner ear. Immune inner-ear disease is a comparatively new area of clinical research, and over time different immunological reactions have been recognized and this has led to the introduction of several laboratory tests in the clinical evaluation of these patients. The pathogenetic mechanisms underlying inner-ear disorders seem to be mainly due to either type 2 cytotoxic interaction of autoantibodies with tissue-bond antigen or a type-3 IgGand IgM-mediated reaction that creates circulating immune complexes. The generic mechanism inducing tissue damage is a specific T-cell clonal expansion, specific autoantibody formation, complement cascade activation with inflammatory cell recruitment. Inner-ear damage and the resultant symptoms could depend upon the type of antigen and tissues as well as the anatomical site involved in the inflammatory reaction, which could be critical in determining endolymphatic hydrops. One of the main issues is the factor that triggers a Tand B-lymphocytes reaction and the production of autoantibodies against inner-ear structure in patients with

Inner ear‐specific autoantibodies

AbstractThe sera of patients with idiopathic sensorineural hearing loss (SNHL) were examined, using qualitative immunoblotting (Western blotting), for the presence of inner ear (IE)‐specific autoantibodies. The water‐soluble extracts and the sodium dodecyl sulfate‐soluble extracts were prepared as the antigens from bovine IE tissues and several other organs in order to determine the specificity of autoantibodies in their sera to the IE. Some patients (n = 46) tested had autoantibodies that reacted with 68‐, 62‐, 55‐, 50‐, or 47‐kd antigenic determinants found in all tissues, while others (n = 13) showed IE‐specific autoantibodies which reacted with 220‐, 60‐, 58‐, 33–35‐, or 32‐kd determinants. The presence of these autoantibodies from patients with progressive SNHL may have important implications with regard to their etiology and possibly their sensitivity to therapeutic intervention. It is now necessary to purify these IE‐specific antigens and determine their clinical usefulness.

Inner ear‐specific autoantibodies

The sera of patients with idiopathic sensorineural hearing loss (SNHL) were examined, using qualitative immunoblotting (Western blotting), for the presence of inner ear (IE)-specific autoantibodies. The water-soluble extracts and the sodium dodecyl sulfate-soluble extracts were prepared as the antigens from bovine IE tissues and several other organs in order to determine the specificity of autoantibodies in their sera to the IE. Some patients (n = 46) tested had autoantibodies that reacted with 68-, 62-, 55-, 50-, or 47-kd antigenic determinants found in all tissues, while others (n = 13) showed IE-specific autoantibodies which reacted with 220-, 60-, 58-, 33-35-, or 32-kd determinants. The presence of these autoantibodies from patients with progressive SNHL may have important implications with regard to their etiology and possibly their sensitivity to therapeutic intervention. It is now necessary to purify these IE-specific antigens and determine their clinical usefulness.

Postnatal developmental changes in inner ear ornithine decarboxylase (ODC)

Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, is important in cellular growth, differentiation and development. Although ODC has been quantitated in cochlear tissues of the adult rat, it has not been assessed quantitatively in developing inner-ear tissues. The purpose of the present study was to quantitate ODC in cochlear tissues of the rat during the period of development of hearing. Cochlear ODC was significantly elevated throughout the period of cochlear maturation in that it increased rapidly during the first 10 days, peaked on day 10 and then declined thereafter. ODC in the lateral wall/organ of Corti tissues was significantly higher than in the cochlear nerve in developing, but not in adult rats. Further examination of separate cochlear tissues from 10-day old rats revealed that ODC activity was higher in the organ of Corti than in the lateral wall or cochlear nerve. Postnatal changes in ODC paralleled functional maturation of hearing and the hypersensitive period for aminoglycoside ototoxicity in the rat. Since aminoglycosides have been shown to inhibit ODC in vitro aminoglycoside inhibition of polyamine synthesis may mediate the hypersensitivity of developing animals to the effects of these drugs.

Decreased Adenosine Triphosphatase Activity in the Absence of Adrenocorticosteroids

Changes in adenosine triphosphatase activity and cellular integrity of rat inner-ear tissues were observed after removal of adrenal steroids via bilateral adrenalectomy. Statistical significance of total and magnesium ion-dependent adenosine triphosphatase activities of the stria vascularis, spiral ligament, and ampullar dark cells from adrenalectomized animals was detected when compared with those of controls as demonstrated by fluorometric microassay. Although there was a similar reduction of activity in utricular dark-cell tissues, no significant difference between the treated and control animals was observed. An increase of intercellular space and a decrease in basolateral infoldings of cells of the stria vascularis and dark cell regions of adrenalectomized animals were observed. Such data collectively provide indirect evidence that adrenal steroids are involved in the cellular regulation of inner-ear tissues that are concerned with fluid and ionic microhomeostasis.