Retracted: Experimental Study of Local Inner Ear Gene Therapy for Controlling Autoimmune Sensorineural Hearing Loss.
Ontology highlight
ABSTRACT:
SUBMITTER: International BR
PROVIDER: S-EPMC5530414 | biostudies-other | 2017
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Although recent advances in magnetic resonance imaging (MRI) techniques have contributed to the detection of tiny lesions in the internal auditory canal (IAC) that may be responsible for sudden sensorineural hearing loss (SSNHL), there have been relatively few studies on the clinical characteristics of intra-labyrinthine hemorrhage (ILH) and labyrinthitis versus those regarding IAC tumors. Our purpose was to investigate the frequency of those IAC lesions on MRI and their clinical characteristics. Initial MRIs of 200 patients with SSNHL (93 men, 107 women; mean age = 48.61 years, range: 18-84 years), as well as detailed clinical histories, audiological examinations, and thyroid function, lipid battery, and serological tests (for viral agents and autoimmune disease), were performed. All patients were hospitalized at the time of diagnosis of SSNHL and were administered the same treatment protocol. Patients were divided into idiopathic and secondary groups according to their MRI results. After discharge, they underwent follow-up audiometry and clinical examination at predetermined intervals (2 weeks, 1, 2, 4, and 6 months, and 1 and 2 years). Propensity score-matching and receiver operating characteristics curves of the initial parameters were used for estimating clinical characteristics. Of the 200 patients, 25 (12.55%) who had abnormal findings suggesting inner ear lesions on MRI were assigned to the secondary SSNHL group; within this group, 10 patients (10/200, 5%) had a tumor invading the IAC, 7 (7/200, 3.5%) had ILH, 6 (6/200, 3%) had labyrinthitis, and 2 (1%) had a structural deformity of the IAC. The secondary group showed significantly poor recovery of hearing function compared with that in the idiopathic group. Patients with ILH or labyrinthitis showed prognoses that were equally poor as those of patients with tumors in the secondary group. Additionally, patients with such lesions showed significant canal paresis on the lesion side at an early stage and a high prevalence of benign paroxysmal positional vertigo (BPPV). In conclusion, the prevalence of non-tumorous lesions on MRI represents common findings and showed a poorer treatment response than that of vestibular Schwannoma in patients with SSNHL. Abnormal canal paresis (cut-off value of 35% on the lesioned side, sensitivity 65.2% and specificity 67%), spontaneous nystagmus directed to the contralesional side, and positional vertigo would be the clinical presentation of SSNHL with IAC lesions, in which the presence of acute prolonged vertigo or positional vertigo compatible with BPPV suggests the possibility of a non-tumorous lesion, such as ILH or a labyrinthitis rather than an IAC tumor.
| S-EPMC5627945 | biostudies-literature
Project description:Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Here we present OTOGL mutations, a homozygous one base pair deletion (c.1430 delT) causing a frameshift (p.Val477Glufs(?)25) in a large consanguineous family and two compound heterozygous mutations, c.547C>T (p.Arg183(?)) and c.5238+5G>A, in a nonconsanguineous family with moderate nonsyndromic sensorineural hearing loss. OTOGL maps to the DFNB84 locus at 12q21.31 and encodes otogelin-like, which has structural similarities to the epithelial-secreted mucin protein family. We demonstrate that Otogl is expressed in the inner ear of vertebrates with a transcription level that is high in embryonic, lower in neonatal, and much lower in adult stages. Otogelin-like is localized to the acellular membranes of the cochlea and the vestibular system and to a variety of inner ear cells located underneath these membranes. Knocking down of otogl with morpholinos in zebrafish leads to sensorineural hearing loss and anatomical changes in the inner ear, supporting that otogelin-like is essential for normal inner ear function. We propose that OTOGL mutations affect the production and/or function of acellular structures of the inner ear, which ultimately leads to sensorineural hearing loss.
| S-EPMC3487139 | biostudies-literature
Project description:There is growing attention and effort focused on treating the root cause of sensorineural hearing loss rather than managing associated secondary characteristic features. With recent substantial advances in understanding sensorineural hearing-loss mechanisms, gene delivery has emerged as a promising strategy for the biological treatment of hearing loss associated with genetic dysfunction. There are several successful and promising proof-of-principle examples of transgene deliveries in animal models; however, there remains substantial further progress to be made in these avenues before realizing their clinical application in humans. Herein, we review different aspects of development, ongoing preclinical studies, and challenges to the clinical transition of transgene delivery of the inner ear toward the restoration of lost auditory and vestibular function. Graphical abstract With recent substantial advances in understanding the mechanisms of sensorineural hearing loss (SNHL), gene therapy has emerged as a promising strategy for its treatment. There are several promising examples of gene therapy in animal models with SNHL; however, substantial advancements need to be made prior to their clinical application.
| S-EPMC8010215 | biostudies-literature
Project description:Osteoprotegerin (OPG) is a key regulator of bone remodeling. Mutations and variations in the OPG gene cause many human diseases that are characterized by not only skeletal abnormalities but also poorly understood hearing loss: Paget's disease, osteoporosis, and celiac disease. To gain insight into the mechanisms of hearing loss in OPG deficiency, we studied OPG knockout (Opg(-/-)) mice. We show that they develop sensorineural hearing loss, in addition to conductive hearing loss due to abnormal middle-ear bones. OPG deficiency caused demyelination and degeneration of the cochlear nerve in vivo. It also activated ERK, sensitized spiral ganglion cells (SGC) to apoptosis, and inhibited proliferation and survival of cochlear stem cells in vitro, which could be rescued by treatment with exogenous OPG, an ERK inhibitor, or bisphosphonate. Our results demonstrate a novel role for OPG in the regulation of SGC survival, and suggest a mechanism for sensorineural hearing loss in OPG deficiency.
| S-EPMC3752395 | biostudies-literature
Project description:Autoimmune and autoinflammatory inner ear diseases (AIED/AID) are characterized by the symptom of sensorineural hearing loss (SNHL). To date, standardized diagnostic tools for AIED/AID are lacking, and clinically differentiating AIED/AID from chronic otitis media (COM) with SNHL is challenging. This retrospective study aimed to construct a magnetic resonance imaging (MRI)-based decision tree using classification and regression tree (CART) analysis to distinguish AIED/AID from COM. In total, 67 patients were enrolled between January 2004 and October 2019, comprising AIED/AID (n = 18), COM (n = 24), and control groups (n = 25). All patients underwent 3 T temporal bone MRI, including post-contrast T1-weighted images (postT1WI) and post-contrast FLAIR images (postFLAIR). Two radiologists evaluated the presence of otomastoid effusion and inner ear contrast-enhancement on MRI. A CART decision tree model was constructed using MRI features to differentiate AIED/AID from COM and control groups, and diagnostic performance was analyzed. High-intensity bilateral effusion (61.1%) and inner ear enhancement (postFLAIR, 93.8%; postT1WI, 61.1%) were the most common findings in the AIED/AID group. We constructed two CART decision tree models; the first used effusion amount as the first partitioning node and postT1WI-inner ear enhancement as the second node, whereas the second comprised two partitioning nodes with the degree of postFLAIR-enhancement of the inner ear. The first and second models enabled distinction of AIED/AID from COM with high specificity (100% and 94.3%, respectively). The amount of effusion and the degree of inner ear enhancement on MRI may facilitate the distinction between AIED/AID and COM with SNHL using decision tree models, thereby contributing to early diagnosis and intervention.
| S-EPMC8476614 | biostudies-literature
Project description:ObjectiveTo describe the progression of sensorineural hearing loss (SNHL) in the better- and poorer-hearing ears in children with asymptomatic congenital cytomegalovirus (CMV) infection with isolated SNHL.Study designLongitudinal prospective cohort study.SettingTertiary medical center.Subjects and methodsWe analyzed hearing thresholds of the better- and poorer-hearing ears of 16 CMV-infected patients with isolated congenital/early-onset or delayed-onset SNHL identified through hospital-based CMV screening of >30,000 newborns from 1982 to 1992.ResultsBy 12 months of age, 4 of 7 patients with congenital/early-onset SNHL developed worsening thresholds in the poorer-hearing ear, and 1 had an improvement in the better-hearing ear. By 18 years of age, all 7 patients had worsening thresholds in the poorer-hearing ear and 3 patients had worsening thresholds in the better-hearing ear. Hearing loss first worsened at a mean age of 2 and 6 years in the poorer- and better-hearing ears, respectively. Nine patients were diagnosed with delayed-onset SNHL (mean age of 9 years vs 12 years for the poorer- and better-hearing ears), 6 of whom had worsening thresholds in the poorer-hearing ear and 1 in both ears.ConclusionIn most children with congenital CMV infection and isolated SNHL, the poorer-hearing ear worsened earlier and more precipitously than the better-hearing ear. This study suggests that monitoring individual hearing thresholds in both ears is important for appropriate interventions and future evaluation of efficacy of antiviral treatment.
| S-EPMC7274837 | biostudies-literature
Project description:[This retracts the article DOI: 10.1155/2014/856019.].
| S-EPMC5530442 | biostudies-other
Project description:Electrophysiological feedback on activity in the auditory pathway may potentially advance the next generation of hearing aids. Conventional electroencephalographic (EEG) systems are, however, impractical during daily life and incompatible with hearing aids. Ear-EEG is a method in which the EEG is recorded from electrodes embedded in a hearing aid like earpiece. The method therefore provides an unobtrusive way of measuring neural activity suitable for use in everyday life. This study aimed to determine whether ear-EEG could be used to estimate hearing thresholds in subjects with sensorineural hearing loss. Specifically, ear-EEG was used to determine physiological thresholds at 0.5, 1, 2, and 4?kHz using auditory steady-state response measurements. To evaluate ear-EEG in relation to current methods, thresholds were estimated from a concurrently recorded conventional scalp EEG. The threshold detection rate for ear-EEG was 20% lower than the detection rate for scalp EEG. Thresholds estimated using in-ear referenced ear-EEG were found to be elevated at an average of 5.9, 2.3, 5.6, and 1.5?dB relative to scalp thresholds at 0.5, 1, 2, and 4?kHz, respectively. No differences were found in the variance of means between in-ear ear-EEG and scalp EEG. In-ear ear-EEG, auditory steady-state response thresholds were found at 12.1 to 14.4?dB sensation level with an intersubject variation comparable to that of behavioral thresholds. Collectively, it is concluded that although further refinement of the method is needed to optimize the threshold detection rate, ear-EEG is a feasible method for hearing threshold level estimation in subjects with sensorineural hearing impairment.
| S-EPMC6291863 | biostudies-literature
Project description:Noise-induced hearing loss (NIHL) is one of the leading causes of sensorineural hearing loss with global importance. The current treatment of choice for patients with hearing problems is a hearing aid or a cochlear implant. However, there is currently no treatment to restore physiological hearing. The development of preventive drugs is currently the focus of hearing research. In order to test the efficacy of a drug, the active ingredient has to be applied at reliable concentrations over a period of time. Osmotic minipumps can provide local drug delivery into the perilymph. Combined with a cochlear implant or a tube, the implantation of the pumps may lead to increased hearing thresholds. Such surgery-related threshold shifts complicate the examination of other factors, such as noise. The aim of the present study was to develop an animal model for the examination of substances that potentially prevent NIHL. For this purpose, six male guinea pigs were unilaterally implanted with a silicon catheter with a hook-shaped microcannula at its tip, attached to an artificial perilymph containing osmotic minipump. One week after surgery, the animals were exposed to four hours of a musical piece, presented at 120 dB SPL, to induce a threshold shift. The implantation of the hook-delivery device caused a moderate threshold shift that allows to detect an additional noise-induced temporary threshold shift. This method enables to investigate drug effects delivered prior to the noise insult in order to establish a preventive strategy against noise-induced temporary threshold shifts. The established drug delivery approach allows the release of drugs into the inner ear in a known concentration and for a known duration. This provides a scientific tool for basic research on drug effects in normal hearing animals.
| S-EPMC9599559 | biostudies-literature
Project description:Peroxisome Biogenesis Disorders (PBD) and Zellweger syndrome spectrum disorders (ZSD) are rare genetic multisystem disorders that include hearing impairment and are associated with defects in peroxisome assembly, function, or both. Mutations in 13 peroxin (PEX) genes have been found to cause PBD-ZSD with ~70% of patients harboring mutations in PEX1. Limited research has focused on the impact of peroxisomal disorders on auditory function. As sensory hair cells are particularly vulnerable to metabolic changes, we hypothesize that mutations in PEX1 lead to oxidative stress affecting hair cells of the inner ear, subsequently resulting in hair cell degeneration and hearing loss. Global deletion of the Pex1 gene is neonatal lethal in mice, impairing any postnatal studies. To overcome this limitation, we created conditional knockout mice (cKO) using Gfi1Creor VGlut3Cre expressing mice crossed to floxed Pex1 mice to allow for selective deletion of Pex1 in the hair cells of the inner ear. We find that Pex1 excision in inner hair cells (IHCs) leads to progressive hearing loss associated with significant decrease in auditory brainstem responses (ABR), specifically ABR wave I amplitude, indicative of synaptic defects. Analysis of IHC synapses in cKO mice reveals a decrease in ribbon synapse volume and functional alterations in exocytosis. Concomitantly, we observe a decrease in peroxisomal number, indicative of oxidative stress imbalance. Taken together, these results suggest a critical function of Pex1 in development and maturation of IHC-spiral ganglion synapses and auditory function.
| S-EPMC9777190 | biostudies-literature