2019年 · 第02卷第02期

Autophagy, a ubiquitous cellular biological behavior that features a lysosome-dependent degradation pathway, is an important mechanism for cellular self-protection in eukaryotes. Autophagy plays essential roles in cell survival, renewal, material reuse and the maintenance of homeostasis. This paper reviews recent advances in understanding the physiological function of autophagy and its possible roles in auditory diseases. We focused our review on original publications on animal models, drug models, and molecular mechanisms of hearing impairment involved in the dysregulation of autophagy. As research on the mechanisms of autophagy has deepened, it has become obvious that autophagy plays essential roles not only in cell survival, but the occurrence and development of a variety of auditory-related disorder, including aminoglycoside-induced hearing loss, age-related hearing loss, and noise-induced hearing loss. While clinical treatment of such conditions via regulation of the development of autophagy is a novel idea, more time is needed to fully elucidate the specific regulatory pathways and modes of autophagy in auditory diseases. The continued study of the mechanisms and regulation of autophagy in auditory diseases will be of great significance for the future treatment and prevention of these conditions.

Hidden hearing loss (HHL), an auditory dysfunction that has gained much recent attention, has the hallmarks of speech discrimination and intelligibility deficits with normal or near-normal hearing thresholds. The pathological mechanisms of HHL are complicated and are not yet fully understood. HHL can be resulted from disorders of the central nervous system such as auditory cortex, and/or pathological changes of inner ear. Thus far, 2 pathological phenomena, synaptopathy and auditory nerve demyelination, have been reported as underlying causes of otogenic HHL. Here, we review the clinical and physiological characteristics of HHL as well as the molecular pathological mechanisms of otogenic HHL and aim to allude to potential therapy targets for clinical applications in the future.

The cochlea plays an important role in the mammalian auditory system. Sound-induced cell motion in the cochlea is transformed into electrical signals that are then sent to primary auditory neurons. The most significant feature of the cochlea is the active and nonlinear amplification of faint sounds. This active process cannot be explained via a simple hydromechanical representation of the cochlea, that is, a macromechanic explanation. Although the mechanisms of this amplification are not well understood, cochlear micromechanical behavior is thought to play a significant role. The measurement of in vivo cochlea micromechanical responses is challenging and restricted by technical limitations. Modeling the micromechanics of the cochlea, however, can facilitate the interpretation of experimental observations. In this paper, we reviewed studies in which researchers modeled the cochlear micromechanics, and we discussed various modeling hypotheses, outcomes, and expectations.

The pathogenic factors of deafness are complex; more than 50% of cases are caused by genetic factors. Between 75% and 80% of cases of hereditary hearing impairment are autosomal recessive, 15% to 25% are autosomal dominant, and 1% to 2% are mitochondrial or X-linked. Cochlea implantation is the main method for treating severe and extremely severe bilateral sensorineural deafness and it is widely used in clinical treatment. As clinical cases of cochlea implantation accumulate, differences in the efficacy of implantation in individuals are emerging and attracting attention. In addition to residual hearing level, implantation age, and other factors, gene mutation is an important factor influencing postoperative rehabilitation in patients. With continuous progress in genetic testing technology for deafness, genetic diagnosis has become an important tool in preoperative evaluation and postoperative effect prediction in patients undergoing cochlear implantation. This article reviews the current status and future development of cochlear implantation in the treatment of hereditary deafness resulting from mutations in common deafness-causing genes.

Cisplatin (CDDP)-induced ototoxicity is one of the common adverse effects of cisplatin chemotherapy. Thus far, effective approaches for attenuating hearing loss are unavailable in clinical practice. Mitochondrial biogenesis acts as a master element of mitochondrial health and is necessary for mitochondrial quality control. The current study examined whether mitochondrial biogenesis is involved in CDDP-induced ototoxicity. Herein, we showed that CDDP damaged mitochondrial function and caused death of House Ear Institute- Organ of Corti 1 (HEI-OC1) cells by impairing mitochondrial biogenesis. Moreover, overexpression of peroxisome proliferator-activated receptor-γ coactivator-1α, a key factor in mitochondrial biogenesis, promoted mitochondrial biogenesis in HEI-OC1 cells and protected them against CDDP-induced cytotoxicity. These findings suggest that mitochondrial biogenesis is involved in the pathology of CDDP cytotoxicity of HEI-OC1 cells, and activation of peroxisome proliferator-activated receptor-γ coactivator-1α can be considered a potential therapeutic strategy to attenuate CDDP-mediated ototoxicity.

Zebrafish have the potential to regrow injured organs and tissues, but their use as a model for hearing regeneration following blast injury has never been reported. In this study, zebrafish were exposed to a blast wave produced by an underwater blast wave generator. The first peak sound pressures produced by this generator were up to 224 dB and 160kPa, measured at 25 cm away from the machine. Zebrafish hearing sensitivity was examined by analyzing auditory evoked potentials from 1 to 35 days post blast wave exposure. Cell death and cell proliferation in inner ear organs, including the saccule, lagena, and utricle, were investigated using a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, and cell proliferation assay using 5-ethynyl-2＇-deoxyuridine, respectively. Significant differences in auditory evoked potential thresholds were observed between exposed and control groups, demonstrating both blast wave-induced hearing loss and recovery of hearing sensitivity. An apoptosis assay revealed significantly increased numbers of terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling- positive cells in the inner ear sensory epithelia of exposed groups compared with the control group. However, numbers of 5-ethynyl- 2＇-deoxyuridine-positive cells in the inner ear of exposed groups recovered to a normal level within 10 post blast wave exposure. Furthermore, blast wave exposure caused brain injury with increased cell apoptosis and decreased neurogenesis. Compared with drug or noise-induced zebrafish models, our blast wave-induced model elicited more serious hearing loss phenotypes, which required more time to return to a normal level. Overall, this zebrafish model can provide a reliable animal model for both hearing loss and regeneration research. The study was approved by the Shanghai 6^th Hospital Animal Care and Use Committee, China (approval No. 2017-0196) on February 28, 2017.

In this retrospective study, we evaluated the preoperative and intraoperative findings and functional results of revision surgery after canal wall down mastoidectomy. We reviewed 34 patients (14 men, 20 women; age, 17–68 years) who underwent revision canal wall down mastoidectomy from March 2006 to March 2017 in the Department of Otology of the First Affiliated Hospital, Wenzhou Medical University, China. This study was approved by the Ethics Committee of the First Affiliated Hospital, Wenzhou Medical University, China (approval No. 2008-05-02A11) on May 2, 2008. The possible reasons for previous surgical failures were confirmed by the operative findings and included a narrow auditory meatus orifice (100%), recurrent or residual cholesteatoma (82%), high facial ridge (94%), residual air cells (47%), and labyrinthine fistula (12%). The mean time until achievement of dry ear after surgery was 5.8 ± 2.4 weeks. After a mean 6-month follow-up, the mean postoperative air–bone gap decreased from 33.8 ± 4.8 to 17.1 ± 5.1 dB in 30 patients who underwent mastoidectomy with simultaneous tympanoplasty. However, no significant postoperative hearing change had occurred in the other 4 patients with eustachian tube occlusion. All patients were followed up for >24 months with a disease-free dry ear and stable hearing results. The main reasons for lack of dry ears after mastoidectomy were a narrow auditory meatus orifice, recurrent or residual cholesteatoma, high facial ridge, and residual air cells. Early dry ear and hearing promotion are obtainable in most patients using revision canal wall down mastoidectomy.