scholarly journals Histopathology of the Human Inner Ear in Alström's Syndrome

2015 ◽  
Vol 20 (4) ◽  
pp. 267-272 ◽  
Author(s):  
Joseph B. Nadol Jr ◽  
Jan D. Marshall ◽  
Roderick T. Bronson
Keyword(s):  
Inner Ear ◽  
Autosomal Recessive ◽  
Ganglion Cells ◽  
Stria Vascularis ◽  
Genetic Disorder ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Spiral Ligament ◽  
Human Inner Ear

Alström's syndrome is an autosomal recessive syndromic genetic disorder caused by mutations in the ALMS1 gene. Sensorineural hearing loss occurs in greater than 85% of patients. Histopathology of the inner ear abnormalities in the human has not previously been fully described. Histopathology of the inner ear in Alström's syndrome is presented in 2 genetically confirmed cases. The predominant histopathologic correlates of the sensorineural loss were degeneration of the organ of Corti, both inner and outer hair cells, degeneration of spiral ganglion cells, and atrophy of the stria vascularis and spiral ligament.

Fine Structure Histopathology of Labyrinthitis Ossificans in the Gerbil Model

2005 ◽  
Vol 114 (2) ◽  
pp. 161-166 ◽  
Author(s):  
Steven P. Tinling ◽  
Vishad Nabili ◽  
Hilary A. Brodie
Keyword(s):  
Connective Tissue ◽  
Ganglion Cells ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Spiral Ligament ◽  
Otic Capsule ◽  
Dense Connective Tissue ◽  
Labyrinthitis Ossificans ◽  
End Stage

Labyrinthitis ossificans (LO) is the pathological deposition of new bone within the lumen of the cochlea and labyrinth. This process occurs most commonly as a result of infection or inflammation affecting the otic capsule. Trauma and vascular compromise can also lead to neo-ossification within the otic capsule. The mechanism that regulates this process remains unestablished. This study details the end-stage histopathology in high-resolution plastic thin sections. Twenty Mongolian gerbils were infected by intrathecal injection of Streptococcus pneumoniae type 3 followed by subcutaneous penicillin G procaine (8 days) and were painlessly sacrificed 3 months later. The cochleas were serially divided and sectioned for light and electron microscopy. Sixteen of 20 animals (27 of 40 cochleas) demonstrated LO. Cochlear damage was most extensive in the vestibule and basal turn and decreased toward the apex, which often appeared normal. The histopathologic findings consisted of 1) new bone, calcospherites, osteoid, and fibrosis without dense connective tissue or osteoblasts extending from the endosteal wall into the lumen of the vestibule and scala tympani; 2) areas of dense connective tissue and osteoid enclosed by epithelial cells conjoined with the organ of Corti, stria vascularis, spiral ligament, and vestibular (Reissner's) membrane; and 3) partial to complete loss of the organ of Corti, spiral ligament cell bodies, stria vascularis, and spiral ganglion cells. Osteoblastic activity was not demonstrated in end-stage ossification in LO in the gerbil model. Neoossification appears to occur by calcospherite deposition along collagen-like fibrils within osteoid. The destruction of the organ of Corti, spiral ganglion cells, stria vascularis, and cells of Reissner's membrane and the spiral ligament occurs even in the absence of ossification of the cochlear duct.

Blebs in inner and outer hair cells: a pathophysiological hypothesis

2008 ◽  
Vol 122 (11) ◽  
pp. 1151-1155 ◽  
Author(s):  
R Ramírez-Camacho ◽  
J R García-Berrocal ◽  
A Trinidad ◽  
J M Verdaguer ◽  
J Nevado
Keyword(s):  
Hair Cells ◽  
Outer Hair Cell ◽  
Ganglion Cells ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Inner Hair Cells ◽  
Hearing Thresholds

AbstractIntroduction:The ototoxic effects of cisplatin include loss of outer hair cells, degeneration of the stria vascularis and a decrease in the number of spiral ganglion cells. Scanning microscopy has shown balloon-like protrusions (blebs) of the plasma membrane of inner hair cells following cisplatin administration. The present study was undertaken to identify the possible role of inner and outer hair cell blebs in the pathogenesis of cisplatin-induced ototoxicity.Materials and methods:Twenty-five guinea pigs were injected with cisplatin and their hearing tested at different time-points, before sacrifice and examination with scanning electron microscopy.Results and analysis:Seven animals showed blebs in the inner hair cells at different stages. Hearing thresholds were lower in animals showing blebs.Discussion:Cisplatin seems to be able to induce changes in inner hair cells as well as in other structures in the organ of Corti. Blebbing observed in animals following cisplatin administration could play a specific role in the regulation of intracellular pressure.

scholarly journals Histopathology of the Human Inner Ear in the p.L114P COCH Mutation (DFNA9)

2016 ◽  
Vol 21 (2) ◽  
pp. 88-97 ◽  
Author(s):  
Barbara J. Burgess ◽  
Jennifer T. O''Malley ◽  
Takefumi Kamakura ◽  
Kris Kristiansen ◽  
Nahid G. Robertson ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Ganglion Cells ◽  
Spiral Ganglion ◽  
Clinical Findings ◽  
Spiral Ligament ◽  
Vestibular Disorder ◽  
Profound Hearing Loss ◽  
The Usa ◽  
Human Inner Ear

The histopathology of the inner ear in a patient with hearing loss caused by the p.L114P COCH mutation and its correlation with the clinical phenotype are presented. To date, 23 COCH mutations causative of DFNA9 autosomal dominant sensorineural hearing loss and vestibular disorder have been reported, and the histopathology of the human inner ear has been described in 4 of these. The p.L114P COCH mutation was first described in a Korean family. We have identified the same mutation in a family of non-Asian ancestry in the USA, and the temporal bone histopathology and clinical findings are presented herein. The histopathology found in the inner ear was similar to that shown in the 4 other COCH mutations and included degeneration of the spiral ligament with deposition of an eosinophilic acellular material, which was also found in the distal osseous spiral lamina, at the base of the spiral limbus, and in mesenchymal tissue at the base of the vestibular neuroepithelium. This is the first description of human otopathology of the COCH p.L114P mutation. In addition, it is the only case with otopathology characterization in an individual with any COCH mutation and residual hearing, thus allowing assessment of primary histopathological events in DFNA9, before progression to more profound hearing loss. A quantitative cytologic analysis of atrophy in this specimen and immunostaining using anti-neurofilament and anti-myelin protein zero antibodies confirmed that the principal histopathologic correlate of hearing loss was degeneration of the dendritic fibers of spiral ganglion cells in the osseous spiral lamina. The implications for cochlear implantation in this disorder are discussed.

scholarly journals Induction of Redox-Active Gene Expression by CoCl2 Ameliorates Oxidative Stress-Mediated Injury of Murine Auditory Cells

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 399 ◽  
Author(s):  
Jhang Ho Pak ◽  
Junyeong Yi ◽  
Sujin Ryu ◽  
In Ki Kim ◽  
Jung-Woong Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ganglion Cells ◽  
Stria Vascularis ◽  
Hypoxia Inducible Factor ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Luciferase Reporter ◽  
Related Factor ◽  
Redox Active

Free radicals formed in the inner ear in response to high-intensity noise, are regarded as detrimental factors for noise-induced hearing loss (NIHL). We reported previously that intraperitoneal injection of cobalt chloride attenuated the loss of sensory hair cells and NIHL in mice. The present study was designed to understand the preconditioning effect of CoCl2 on oxidative stress-mediated cytotoxicity. Treatment of auditory cells with CoCl2 promoted cell proliferation, with increases in the expressions of two redox-active transcription factors (hypoxia-inducible factor 1α, HIF-1α, nuclear factor erythroid 2-related factor 2; Nrf-2) and an antioxidant enzyme (peroxiredoxin 6, Prdx6). Hydrogen peroxide treatment resulted in the induction of cell death and reduction of these protein expressions, reversed by pretreatment with CoCl2. Knockdown of HIF-1α or Nrf-2 attenuated the preconditioning effect of CoCl2. Luciferase reporter analysis with a Prdx6 promoter revealed transactivation of Prdx6 expression by HIF-1α and Nrf-2. The intense immunoreactivities of HIF-1α, Nrf-2, and Prdx6 in the organ of Corti (OC), spiral ganglion cells (SGC), and stria vascularis (SV) of the cochlea in CoCl2-injected mice suggested CoCl2-induced activation of HIF-1α, Nrf-2, and Prdx6 in vivo. Therefore, we revealed that the protective effect of CoCl2 is achieved through distinctive signaling mechanisms involving HIF-1α, Nrf-2, and Prdx6.

scholarly journals Otic Pathology of Caprine β-Mannosidosis

1988 ◽  
Vol 25 (6) ◽  
pp. 437-442 ◽  
Author(s):  
J. A. Render ◽  
K. L. Lovell ◽  
M. Z. Jones
Keyword(s):  
Storage Disease ◽  
Stria Vascularis ◽  
Genetic Disorder ◽  
Spiral Ganglion ◽  
Clinical Signs ◽  
Organ Of Corti ◽  
Scala Tympani ◽  
Electron Microscopic ◽  
Middle Ear Mucosa ◽  
Cochlear Hair Cells

Caprine β-mannosidosis is an autosomal recessive defect of glycoprotein catabolism with a deficiency of tissue and plasma β-mannosidase activity and tissue accumulation of oligosaccharides within lysosomes. This rapidly fatal genetic disorder of Nubian goats is expressed at birth by a variety of clinical signs including deafness. Affected goats had folded pinnas, and the tympanic cavity was decreased due to multiple, polypoid projections of bone covered by middle ear mucosa which obstructed the view of the cochlear promontory. Numerous cells of the cochlear duct including mesothelial and epithelial cells of Reissner's membrane, mesothelial cells lining the scala tympani, cells of the stria vascularis, numerous supportive cells of the organ of Corti, cochlear hair cells, endothelial cells, perithelial cells, fibroblasts, macrophages, and neurons of the spiral ganglion contained numerous nonstaining intracytoplasmic vacuoles which resulted in distention of affected cells and caused thickening of involved structures. Ultrastructurally, the vacuoles were membrane-bound and consistent with lysosomes. Vacuolated cells were desquamated into the scala vestibuli and scala tympani. This is one of few reports describing light and electron microscopic otic alterations of a storage disease. Goats with β-mannosidosis appear to be good models of hearing loss in patients with storage disease.

scholarly journals NTPDase1 and NTPDase2 Immunolocalization in Mouse Cochlea: Implications for Regulation of P2 Receptor Signaling

2002 ◽  
Vol 50 (11) ◽  
pp. 1435-1441 ◽  
Author(s):  
Srdjan M. Vlajkovic ◽  
Peter R. Thorne ◽  
Jean Sévigny ◽  
Simon C. Robson ◽  
Gary D. Housley
Keyword(s):  
Hair Cells ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Nerve Fibers ◽  
Outer Hair Cells ◽  
Spiral Ligament ◽  
Receptor Signaling ◽  
P2 Receptor ◽  
Efferent Nerve ◽  
Root Region

Cellular, molecular, and physiological studies have demonstrated an important signaling role for ATP and related nucleotides acting via P2 receptors in the cochlea of the inner ear. Signal modulation is facilitated by ectonucleotidases, a heterologous family of surface-located enzymes involved in extracellular nucleotide hydrolysis. Our previous studies have implicated CD39/NTPDase1 and CD39L1/NTPDase2, members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family, as major ATP-hydrolyzing enzymes in the tissues lining the cochlear endolymphatic and perilymphatic compartments. NTPDase1 hydrolyzes both nucleoside triphosphates and diphosphates. In contrast, NTPDase2 is a preferential nucleoside triphosphatase. This study characterizes expression of these E-NTPDases in the mouse cochlea by immunohistochemistry. NTPDase1 can be immunolocalized to the cochlear vasculature and neural tissues (primary auditory neurons in the spiral ganglion). In contrast, NTPDase2 immunolabeling was principally localized to synaptic regions of the sensory inner and outer hair cells, stereocilia and cuticular plates of the outer hair cells, supporting cells of the organ of Corti (Deiters’ cells and inner border cells), efferent nerve fibers located in the intraganglionic spiral bundle, and in the outer sulcus and root region of the spiral ligament. This differential expression of NTPDase1 and 2 in the cochlea suggests spatial regulation of P2 receptor signaling, potentially involving different nucleotide species and hydrolysis kinetics.

scholarly journals Cochlear protein biomarkers as potential sites for targeted inner ear drug delivery

2019 ◽  
Vol 10 (2) ◽  
pp. 368-379
Author(s):  
James G. Naples ◽  
Lauren E. Miller ◽  
Andrew Ramsey ◽  
Daqing Li
Keyword(s):  
Drug Delivery ◽  
Inner Ear ◽  
Ganglion Cells ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Cell Types ◽  
Protein Biomarkers ◽  
Single Location ◽  
Specific Manner ◽  
The Many

AbstractThe delivery of therapies to the cochlea is notoriously challenging. It is an organ protected by a number of barriers that need to be overcome in the drug delivery process. Additionally, there are multiple sites of possible damage within the cochlea. Despite the many potential sites of damage, acquired otologic insults preferentially damage a single location. While progress has been made in techniques for inner ear drug delivery, the current techniques remain non-specific and our ability to deliver therapies in a cell-specific manner are limited. Fortunately, there are proteins specific to various cell-types within the cochlea (e.g., hair cells, spiral ganglion cells, stria vascularis) that function as biomarkers of site-specific damage. These protein biomarkers have potential to serve as targets for cell-specific inner ear drug delivery. In this manuscript, we review the concept of biomarkers and targeted- inner ear drug delivery and the well-characterized protein biomarkers within each of the locations of interest within the cochlea. Our review will focus on targeted drug delivery in the setting of acquired otologic insults (e.g., ototoxicity, noise-induce hearing loss). The goal is not to discuss therapies to treat acquired otologic insults, rather, to establish potential concepts of how to deliver therapies in a targeted, cell-specific manner. Based on our review, it is clear that future of inner ear drug delivery is a discipline filled with potential that will require collaborative efforts among clinicians and scientists to optimize treatment of otologic insults.

scholarly journals The Role of Thiamine Pyrophosphate in Prevention of Cisplatin Ototoxicity in an Animal Model

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Ozan Kuduban ◽  
Cuneyt Kucur ◽  
Ebru Sener ◽  
Halis Suleyman ◽  
Fatih Akcay
Keyword(s):  
Guinea Pigs ◽  
Intraperitoneal Injection ◽  
Ganglion Cells ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Outer Hair Cells ◽  
Thiamine Pyrophosphate ◽  
Control Group ◽  
Group 2 ◽  
Group 1

Objective. The aim of this study was to evaluate the effectiveness of thiamine pyrophosphate against cisplatin-induced ototoxicity in guinea pigs.Materials and Methods. Healthy guinea pigs (n=18) were randomly divided into three groups. Group 1 (n=6) received an intraperitoneal injection of saline solution and cisplatin for 7 days, group 2 (n=6) received an intraperitoneal injection of thiamine pyrophosphate and cisplatin for 7 days, and group 3 (n=6) received only intraperitoneal injection of saline for 7 days. The animals in all groups were sacrificed under anesthesia, and their cochleas were harvested for morphological and biochemical observations.Results. In group 1, receiving only cisplatin, cochlear glutathione concentrations, superoxide dismutase, and glutathione peroxidase activities significantly decreased (P<0.05) and malondialdehyde concentrations significantly increased (P<0.05) compared to the control group. In group 2, receiving thiamine pyrophosphate and cisplatin, the concentrations of enzymes were near those of the control group. Microscopic examination showed that outer hair cells, spiral ganglion cells, and stria vascularis were preserved in group 2.Conclusion. Systemic administration of thiamine pyrophosphate yielded statistically significant protection to the cochlea of guinea pigs from cisplatin toxicity. Further experimental animal studies are essential to determine the appropriate indications of thiamine pyrophosphate before clinical use.

scholarly journals ADAMTS1, MPDZ, MVD, and SEZ6: candidate genes for autosomal recessive nonsyndromic hearing impairment

2021 ◽  
Author(s):  
Thashi Bharadwaj ◽  
Isabelle Schrauwen ◽  
Sakina Rehman ◽  
Khurram Liaqat ◽  
Anushree Acharya ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Inner Ear ◽  
Candidate Genes ◽  
Hearing Impairment ◽  
In Silico ◽  
Autosomal Recessive ◽  
Ganglion Cells ◽  
Spiral Ganglion ◽  
In Silico Analysis ◽  
Sensory Epithelium

AbstractHearing impairment (HI) is a common disorder of sensorineural function with a highly heterogeneous genetic background. Although substantial progress has been made in the understanding of the genetic etiology of hereditary HI, many genes implicated in HI remain undiscovered. Via exome and Sanger sequencing of DNA samples obtained from consanguineous Pakistani families that segregate profound prelingual sensorineural HI, we identified rare homozygous missense variants in four genes (ADAMTS1, MPDZ, MVD, and SEZ6) that are likely the underlying cause of HI. Linkage analysis provided statistical evidence that these variants are associated with autosomal recessive nonsyndromic HI. In silico analysis of the mutant proteins encoded by these genes predicted structural, conformational or interaction changes. RNAseq data analysis revealed expression of these genes in the sensory epithelium of the mouse inner ear during embryonic, postnatal, and adult stages. Immunohistochemistry of the mouse cochlear tissue, further confirmed the expression of ADAMTS1, SEZ6, and MPDZ in the neurosensory hair cells of the organ of Corti, while MVD expression was more prominent in the spiral ganglion cells. Overall, supported by in silico mutant protein analysis, animal models, linkage analysis, and spatiotemporal expression profiling in the mouse inner ear, we propose four new candidate genes for HI and expand our understanding of the etiology of HI.

Morphologic Effects of Glycerol and Urea on Cochlear Tissues of the Chinchilla

1988 ◽  
Vol 97 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Charles G. Wright ◽  
David H. Lee ◽  
William L. Meyerhoff ◽  
Peter S. Roland
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Endolymphatic Hydrops ◽  
Stria Vascularis ◽  
Metabolic Stress ◽  
Mechanisms Of Action ◽  
Outer Hair Cells ◽  
Ultrastructural Changes ◽  
Spiral Ligament ◽  
Subcutaneous Injections

Glycerol and urea are used as test agents in confirming the diagnosis of endolymphatic hydrops. Although both substances act as osmotic diuretics, recent evidence suggests that they may have differing physiologic effects on the inner ear. This study was designed to compare the morphologic effects of urea and glycerol on cochlear tissues, using the chinchilla as an experimental model. Animals were given subcutaneous injections of glycerol (2 g/kg) or urea (1.2 g/kg) over periods of 3 hours, 4 days, or 1 week. Both agents were found to produce ultrastructural changes, including spiral ligament vacuolization, intracellular alterations of the stria vascularis, and increased numbers of Hensen's bodies in outer hair cells. These alterations appeared indicative of metabolic stress, but not toxicity. The morphologic findings provided no evidence that glycerol and urea affect the inner ear by fundamentally different mechanisms of action.

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