Hearing Research最新文献

{"title":"The therapeutic effect and underlying biochemical mechanism of methylprednisolone and D-methionine in “rescuing” noise-induced hearing loss in guinea pigs","authors":"Po-Hsuan Wu ,&nbsp;Wu-Chia Lo ,&nbsp;Chih-Ming Chang ,&nbsp;Po-Wen Cheng ,&nbsp;Shing-Hwa Liu","doi":"10.1016/j.heares.2024.109148","DOIUrl":"10.1016/j.heares.2024.109148","url":null,"abstract":"<div><h3>Objectives</h3><div>Currently, there are no approved therapeutics for noise-induced hearing loss (NIHL). Both oxidative stress and cochlear inflammation play important roles in the mechanism of NIHL. In this study, we evaluate the effect of D-methionine (D-met) and methylprednisolone (MP) on noise-induced hearing loss of guinea pigs.</div></div><div><h3>Design</h3><div>One hundred and thirty-two male guinea pigs were evenly divided into eleven groups: control, saline, MP (15, 30, 45 mg/kg), D-met (200, 400, 600 mg/kg), and combinations of MP (15, 30, 45 mg/kg) with D-met (200, 400, 600 mg/kg) in increasing doses. Sixty minutes following a 6-hour exposure to continuous broadband white noise at a sound pressure level of 105 ± 2 dB, treatments were given every 12 h over the course of 3 days. Click-evoked auditory brainstem responses were evaluated one day before and fourteen days after noise exposure. The animals in the combination group were sacrificed 14 days after noise exposure, and cochlear lateral wall Na⁺, K⁺-ATPase and Ca²⁺-ATPase activities, and lipid peroxidation (LPO) were evaluated.</div></div><div><h3>Results</h3><div>The mean permanent threshold shift (PTS) showed a dose-dependent rescue effect from low to high doses in both MP and D-met treatment groups. In the combination treatment groups, MP (45 mg/kg) with D-met (600 mg/kg) demonstrated a complete rescue response without a significant difference in PTS compared to the control group. The noise-induced decreases in Na⁺, K⁺-ATPase and Ca²⁺-ATPase activities demonstrated dose-dependent recoveries from the low to high dose combination groups. Specifically, the MP (45 mg/kg) with D-met (600 mg/kg) group achieved 84.8% and 95.5% recovery of Na⁺, K⁺-ATPase and Ca²⁺-ATPase activity levels, respectively, compared to the control group. The noise-induced increase in LPO levels exhibited dose-dependent alleviation from the low to high dose combination groups, showing only a 12.3% LPO increment in the MP (45 mg/kg) with D-met (600 mg/kg) group.</div></div><div><h3>Conclusions</h3><div>Noise-induced hearing loss was completely rescued in the MP (45 mg/kg) with D-met (600 mg/kg) treatment group. Significant decreases in cochlear lateral wall oxidative stress were demonstrated, along with the reversal of Na⁺, K⁺-ATPase and Ca²⁺-ATPase activity levels.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"454 ","pages":"Article 109148"},"PeriodicalIF":2.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired brainstem auditory evoked potentials after in utero exposure to high dose paracetamol exposure","authors":"Meghan Graeca,&nbsp;Randy Kulesza","doi":"10.1016/j.heares.2024.109149","DOIUrl":"10.1016/j.heares.2024.109149","url":null,"abstract":"<div><div>Paracetamol is an analgesic and antipyretic medication regarded as the safest over-the-counter pain and fever relief option during pregnancy. Paracetamol and its metabolites are known to reach the developing fetus through direct placental transfer and can cross the blood brain barrier. Several recent, large-scale epidemiologic studies suggest that <em>in utero</em> paracetamol exposure can increase the risk of neurodevelopmental conditions, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and developmental delay (DD). Since auditory processing deficits are a common feature of ASD, we hypothesized that animals exposed to paracetamol <em>in utero</em> will have impaired auditory brainstem function. We investigated this hypothesis by recording and analyzing click-evoked auditory brainstem responses (ABR) at postnatal day 21 and 29 in Sprague-Dawley rats. <em>In utero</em> exposure to high dose paracetamol exposure had no impact on body or brain weight. However, high dose paracetamol exposure did significantly delay ear opening and resulted in elevated ABR thresholds, and longer wave and interwave latencies. These changes in wave latency extended to the highest click intensity tested but were most severe near threshold. This data suggests that development and function of the auditory brainstem may be impacted by high dose paracetamol exposure and that simple, non-invasive tests of auditory function have utility as an early screening tool for neurodevelopmental disorders.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"454 ","pages":"Article 109149"},"PeriodicalIF":2.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silicone-based AC102-loaded cochlear implant coatings protect residual hearing in an animal model of cochlear implantation","authors":"Michael Nieratschker ,&nbsp;Pavel Mistrik ,&nbsp;Zdenek Petrasek ,&nbsp;Erdem Yildiz ,&nbsp;Anselm J. Gadenstaetter ,&nbsp;Matthias Gerlitz ,&nbsp;Anne-Margarethe Kramer ,&nbsp;Monika Kwiatkowska ,&nbsp;Susanne Braun ,&nbsp;Reimar Schlingensiepen ,&nbsp;Clemens Honeder ,&nbsp;Christoph Arnoldner","doi":"10.1016/j.heares.2024.109150","DOIUrl":"10.1016/j.heares.2024.109150","url":null,"abstract":"<div><div>Cochlear implant users with residual hearing benefit synergistically from combined electrical stimulation via the cochlear implant and preserved residual hearing after surgery. However, direct mechanical trauma and subsequent inflammation may deteriorate hearing function. AC102, a novel otoprotective pyridoindole with anti-apoptotic and anti-oxidative properties significantly improved hearing recovery following cochlear implantation when administered intratympanically prior to surgery. Additionally, AC102 exerts neurotrophic effects, possibly aiding in the preservation of auditory nerve fibers and spiral ganglion neurons. Rapid clearance of the drug, however, might be a limiting factor to further attenuate the inflammatory response and maintain neuronal health. The aim of the current study was to design an AC102-loaded electrode array for sustained drug delivery and investigate its effects in hearing preservation cochlear implantation.</div><div>First, the release-kinetics of AC102 were investigated <em>in vitro</em> and modelled by the Higuchi equation of drug release. An electrode array coated with 10 % AC102 was manufactured, its release kinetics evaluated, and subsequently tested <em>in vivo</em>. 20 normal hearing Mongolian gerbils were unilaterally implanted with an AC102-loaded or an unloaded control electrode. Compound action potentials were measured prior to cochlear implantation and serially over 28 days. Hair cells, inner hair cell synapses, and auditory nerve fibers were quantified in cochlear whole-mounts by immunofluorescence staining.</div><div>AC102 release from silicone coating could be predictably modelled by the Higuchi equation of drug release. The electrode array with an AC102-silicone depot enabled non-linear sustained drug release with initially higher release concentrations. <em>In vivo</em>, the AC102-loaded electrode array significantly recovered auditory threshold shifts near the maximum insertion depth over 28 days. In the apical region, a significant recovery was noticed only until day 14, after which threshold shifts aligned between groups. Histologically, AC102-loaded electrodes significantly preserved outer hair cells apical of the maximum insertion depth and inner hair cells and neuronal structures at the tip of the inserted electrode.</div><div>In conclusion, the drug-loaded electrode arrays could predictably release AC102 over a period of 28 days. AC102 enabled the restoration of auditory thresholds near the area of maximum insertion, which is the desired region to be preserved in cochlear implant recipients with residual hearing.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"454 ","pages":"Article 109150"},"PeriodicalIF":2.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensory and affective dimensions in loudness perception: Insights from young adults","authors":"Charlotte Bigras ,&nbsp;Victoria Duda ,&nbsp;Sylvie Hébert","doi":"10.1016/j.heares.2024.109147","DOIUrl":"10.1016/j.heares.2024.109147","url":null,"abstract":"<div><div>Traditional psychoacoustic measures often lack accuracy in diagnosing hyperacusis and other sound tolerance disorders, possibly due to their reliance on artificial stimuli and unidimensional scales. The aim of this study was to assess loudness across sensory and affective dimensions using natural sounds, drawing on pain research wherein intensity and unpleasantness are assessed separately. We hypothesized that similar distinctions apply to loudness perception. A total of 102 young adults with normal to mild hearing loss rated 32 sound stimuli (pleasant, unpleasant, neutral, and artificial) at 10 intensities (40 to 100 dBA) on sensory and affective scales. They also completed the Hyperacusis Questionnaire, the Noise Sensitivity Scale, and the Hospital Anxiety and Depression Scale. Mixed linear models indicated both correlations and dissociations between scales that varied according to intensity and valence. Louder stimuli were rated as more unpleasant, but only at high intensities. On the sensory scale, sounds were perceived as louder with increasing intensity; however, at low to moderate intensities, pleasant and neutral sounds were rated as louder, whereas at higher intensities, artificial and unpleasant stimuli were rated as louder. On the affective scale, the perception of unpleasantness also increased with intensity, but less steeply. At high intensities, artificial stimuli were rated similarly to unpleasant stimuli. Noise sensitivity scores predicted louder and more unpleasant ratings, whereas depression scores were associated with softer and less pleasant perceptions. This study highlights the need for multidimensional approaches in audiology and suggests that the integration of sensory and affective scales with natural stimuli may improve the diagnosis and treatment of sound tolerance disorders.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"454 ","pages":"Article 109147"},"PeriodicalIF":2.5,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the phase consistency of apical organ of Corti vibrations","authors":"George W.S. Burwood ,&nbsp;Tianying Ren ,&nbsp;Alfred L. Nuttall ,&nbsp;Anders Fridberger","doi":"10.1016/j.heares.2024.109137","DOIUrl":"10.1016/j.heares.2024.109137","url":null,"abstract":"<div><div>Low-frequency hearing is critically important for speech and music perception. However, technical and anatomical limitations previously made it difficult to study the mechanics of the low-frequency parts of the cochlea, but this changed with the introduction of optical coherence tomography vibrometry. With this technique, sound-evoked vibration can be measured from the apex of a fully intact cochlea. Results of such measurements generated controversy because conventional traveling waves, the hallmark of which is longer group delay closer to the helicotrema, were absent within the apical 20% of the guinea pig cochlea (Burwood <em>et al</em>, Science Advances 8:eabq2773, 2022). The validity of this result was questioned, primarily because group delays were calculated from phase values averaged across many points within the organ of Corti. Here we show that variations in phase across the organ of Corti are minor and does not affect the group delay significantly. We also assess the precision of phase measurements with optical coherence tomography. An artificial target with reflectivity similar to the organ of Corti was used. These measurements revealed that a commonly used commercial optical coherence tomography system produces half-cycle errors in 1-5 % of pixels, leading to a bimodal distribution of phase values. This problem can be easily addressed by using medians when computing averages, as was done by Burwood <em>et al</em> (2022). Hence, neither averaging across pixels nor technical factors can explain the apparent lack of conventional traveling waves at the apex of the guinea pig cochlea at low stimulus levels. The physiological mechanisms that operate at the apex apparently differ from other cochlear regions.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"454 ","pages":"Article 109137"},"PeriodicalIF":2.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phoneme-related potentials recorded from normal hearing listeners and cochlear implant users in a selective attention paradigm to continuous speech","authors":"Nina Aldag,&nbsp;Waldo Nogueira","doi":"10.1016/j.heares.2024.109136","DOIUrl":"10.1016/j.heares.2024.109136","url":null,"abstract":"<div><div>Cochlear implants can restore the ability to understand speech in patients with profound sensorineural hearing loss. At present, it is not fully understood how cochlear implant users perceive speech and how electric hearing provided by a cochlear implant differs from acoustic hearing. Phoneme-related potentials characterize neural responses to individual instances of phonemes extracted from continuous speech.</div><div>This retrospective study investigated phoneme-related potentials in cochlear implant users in a selective attention paradigm. Responses were compared between normal hearing listeners and cochlear implant users, and between attended and unattended conditions. Differences between phoneme categories were compared and a classifier was trained to predict the phoneme category from the neural representation.</div><div>The phoneme-related potentials of cochlear implant users showed similar responses to the ones obtained in normal hearing listeners for early responses (&lt; 100 ms) but not for later responses (&gt; 100 ms) where peaks were smaller or absent. Attention led to an enhancement of the response, whereas latency was mostly not affected by attention. The temporal morphology of the response was influenced by the phonetic features of the stimulus, allowing a classification of the phoneme category based on the phoneme-related potentials.</div><div>There is a clinical need for methods that can rapidly and objectively assess the speech understanding performance of cochlear implant users. Phoneme-related potentials may provide such a link between the acoustic and the neural representations of phonemes. They may also reveal the challenges of individual subjects and thus provide indications for patient-specific auditory training, rehabilitation programs or the fitting of cochlear implant parameters.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"454 ","pages":"Article 109136"},"PeriodicalIF":2.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vocal control and speech production in cochlear implant listeners: A review within auditory-motor processing framework","authors":"Samin Ashjaei ,&nbsp;Roozbeh Behroozmand ,&nbsp;Shaivee Fozdar ,&nbsp;Reed Farrar ,&nbsp;Meisam Arjmandi","doi":"10.1016/j.heares.2024.109132","DOIUrl":"10.1016/j.heares.2024.109132","url":null,"abstract":"<div><div>A comprehensive literature review is conducted to summarize and discuss prior findings on how cochlear implants (CI) affect the users’ abilities to produce and control vocal and articulatory movements within the auditory-motor integration framework of speech. Patterns of speech production pre- versus post-implantation, post-implantation adjustments, deviations from the typical ranges of speakers with normal hearing (NH), the effects of switching the CI on and off, as well as the impact of altered auditory feedback on vocal and articulatory speech control are discussed. Overall, findings indicate that CIs enhance the vocal and articulatory control aspects of speech production at both segmental and suprasegmental levels. While many CI users achieve speech quality comparable to NH individuals, some features still deviate in a group of CI users even years post-implantation. More specifically, contracted vowel space, increased vocal jitter and shimmer, longer phoneme and utterance durations, shorter voice onset time, decreased contrast in fricative production, limited prosodic patterns, and reduced intelligibility have been reported in subgroups of CI users compared to NH individuals. Significant individual variations among CI users have been observed in both the pace of speech production adjustments and long-term speech outcomes. Few controlled studies have explored how the implantation age and the duration of CI use influence speech features, leaving substantial gaps in our understanding about the effects of spectral resolution, auditory rehabilitation, and individual auditory-motor processing abilities on vocal and articulatory speech outcomes in CI users. Future studies under the auditory-motor integration framework are warranted to determine how suboptimal CI auditory feedback impacts auditory-motor processing and precise vocal and articulatory control in CI users.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"453 ","pages":"Article 109132"},"PeriodicalIF":2.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic tinnitus is associated with aging but not dementia","authors":"Lisa Reisinger ,&nbsp;Nathan Weisz","doi":"10.1016/j.heares.2024.109135","DOIUrl":"10.1016/j.heares.2024.109135","url":null,"abstract":"<div><h3>Aim</h3><div>Aging is related to deterioration of bodily and neural functions, leading to various disorders and symptoms, including the development of dementia, hearing loss, or tinnitus. Understanding how these phenomena are intertwined and how aging affects those is crucial for prevention and the future development of interventions.</div></div><div><h3>Methods</h3><div>We utilized the UK Biobank which includes a total of 502,382 participants between 40 and 70 years old. We used logistic regression models and cox proportional hazard models and compared hazard ratios.</div></div><div><h3>Results</h3><div>The odds of reporting tinnitus in the older age group (i.e., older than 58 years) were increased by 53.6 % and a one decibel increase in the speech-reception thresholds enhanced the odds for tinnitus by 13.0 %. For our second analysis regarding hearing loss, the risk of dementia increased by 14.0 % with an increase by one decibel in the speech-reception threshold score. In terms of aging, each additional year increased the risk by 17.3 %. Tinnitus alone showed a significant influence with a hazard ratio of 52.1 %, however, when adding hearing loss, age and various covariates, the effect vanished.</div></div><div><h3>Conclusion</h3><div>Findings confirm that tinnitus is indeed related to aging, but presumably independent of the aging processes accompanying the development of dementia. This highlights the urge to further investigate the impact of aging on neural processes that are relevant for alterations in the auditory systems (e.g., leading to the development of tinnitus or hearing loss) as well as for increased vulnerability in terms of neurodegenerative diseases.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"453 ","pages":"Article 109135"},"PeriodicalIF":2.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical role of hepsin/TMPRSS1 in hearing and tectorial membrane morphogenesis: Insights from transgenic mouse models","authors":"Ting-Hua Yang ,&nbsp;Yu-Chen Hsu ,&nbsp;Peng Yeh ,&nbsp;Chia-Jui Hung ,&nbsp;Yu-Fei Tsai ,&nbsp;Mo-Chu Fang ,&nbsp;Alice Chih Chia Yen ,&nbsp;Li-Fu Chen ,&nbsp;Jhih-Yu Pan ,&nbsp;Chen-Chi Wu ,&nbsp;Tien-Chen Liu ,&nbsp;Fong-Ling Chung ,&nbsp;Wei-Ming Yu ,&nbsp;Shu-Wha Lin","doi":"10.1016/j.heares.2024.109134","DOIUrl":"10.1016/j.heares.2024.109134","url":null,"abstract":"<div><div>Mutations in various type II transmembrane serine protease (TMPRSS) family members are associated with non-syndromic hearing loss, with some mechanisms still unclear. For instance, the mechanism underlying profound hearing loss and tectorial membrane (TM) malformations in hepsin/TMPRSS1 knockout (KO) mice remains elusive. In this study, we confirmed significantly elevated hearing thresholds and abnormal TM morphology in hepsin KO mice, characterized by enlarged TM with gaps and detachment from the spiral limbus. Transgenic mouse lines were created to express either wild-type or a serine protease-dead mutant of human hepsin in the KO background. The Tg68;KO line, expressing moderate levels of wild-type human hepsin in the cochlea, showed partial restoration of hearing function. Conversely, the Tg5;KO or TgRS;KO lines, with undetectable hepsin or protease-dead hepsin, did not show such improvement. Histological analyses revealed that Tg68;KO mice, but not Tg5;KO or TgRS;KO mice, had a more compact TM structure, partially attached to the spiral limbus. These results indicate that hepsin expression levels correlate with improvements in hearing and TM morphology, and its protease activity is critical for these effects. Hepsin's role was further examined by studying its relationship with α-tectorin (TECTA) and β-tectorin (TECTB), non-collagenous proteins crucial for TM formation. Hepsin was co-expressed with TECTA and TECTB in the developing cochlear epithelium. Immunostaining showed decreased levels of TECTA and TECTB in hepsin KO TM, partially restored in Tg68;KO mice. These findings suggest that hepsin is essential for proper TM morphogenesis and auditory function, potentially by proteolytic processing/maturation of TECTA and TECTB and their incorporation into the TM.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"453 ","pages":"Article 109134"},"PeriodicalIF":2.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene therapy for hearing loss: Current status and future prospects of non-viral vector delivery systems","authors":"Jean-Christophe Leclère ,&nbsp;Remi Marianowski ,&nbsp;Tristan Montier","doi":"10.1016/j.heares.2024.109130","DOIUrl":"10.1016/j.heares.2024.109130","url":null,"abstract":"<div><div>Current therapeutic options for hearing loss rely on hearing aids, ossiculoplasty or cochlear implants. These devices have limitations, particularly in noisy acoustic environments. Therefore, interest in exploring aetiological treatments to improve not only auditory perception but also the quality of life of those affected is increasing. Gene therapy is a promising aetiological treatment that can fully restore auditory function. The success of gene therapy relies on the efficient delivery of therapeutic genes or genetic modifications to the cells of the inner ear that are designed to repair or replace defective genes and restore normal hearing function. Two main strategies for gene therapy involve the use of recombinant viral vectors and nonviral delivery vehicles.</div><div>Owing to their excellent diffusion properties and compatibility with sensory cells, recombinant viral vectors, particularly adeno-associated viruses (AAVs), have dominated gene therapy in the cochlea. However, recombinant viral vectors have several drawbacks, such as limited transgene size, immunogenicity (particularly in neonates), and potential need for repeat administration.</div><div>Nonviral vectors, such as cationic lipids and polymeric nanoparticles, are potential attractive alternatives. Nonviral vectors have several advantages, including low immunogenicity and unlimited transgene size. Recent studies have demonstrated significant auditory recovery in vivo using nonviral vectors in murine models. However, nonviral vectors are not as efficient as viral vectors in transferring genetic material.</div><div>An alternative to nanoparticles is the use of other methods, such as electroporation. The main advantage of electroporation is that it can be used in combination with cochlear implantation and can target surface cells, but this method has a risk of cell damage.</div><div>The goal of this review is to provide valuable insights into the current state of research on nonviral vectors for inner ear gene therapy and propose the exploration of innovative and effective gene therapy strategies for the treatment of hearing loss.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"453 ","pages":"Article 109130"},"PeriodicalIF":2.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}