Ménière's disease and allergy: Epidemiology, pathogenesis, and therapy.

The etiology of Ménière's disease (MD) remains controversial. Allergies are potential extrinsic factors that, in conjunction with underlying intrinsic factors, may cause MD. The link between allergies and MD was first described in 1923. For nearly a century, studies have demonstrated a possible link between allergies and MD, even though a causal relationship has not been definitively determined. Previous reviews have mainly focused on clinical epidemiology studies of patients. In this review, we shed light on the association between allergies and MD not only in terms of its epidemiology, but also from an immunology, pathophysiology, and immunotherapy perspective in both patients and animal models. Patients with MD tend to have a high risk of comorbid allergies or an allergy history, showing positive allergy immunology characteristics. Other MD-related diseases, such as migraine, may also interact with allergies. Allergy mediators such as IgE may worsen the symptoms of MD. Deposits of IgE in the vestibular end organs indicate the ability of the inner ear to participate in immune reactions. Allergic challenges can induce vertigo in animals and humans. Anti-allergy therapy plays a positive role in patients with MD and animal models of endolymphatic hydrops.

Ménière's disease is a disorder of the inner ear.

PURPOSE OF REVIEW: Ménière's disease is a disorder characterized by recurrent episodes of vertigo, hearing loss, tinnitus, and pressure in the ear. Its pathogenesis and optimal management continue to be the subject of ongoing debate. Although it is classically believed to be a primary disorder of the inner ear, some clinicians have hypothesized that it is a form of vestibular migraine. RECENT FINDINGS: Evidence supporting vestibular migraine in the differential of Ménière's disease includes overlap of symptoms, high prevalence of migraines in patients with Ménière's disease, and the efficacy of migraine treatments for symptoms of Ménière's disease in some patients. However, there is far more evidence to support Ménière's disease as a disorder of the inner ear, including genetic and histologic changes of hydrops, imaging studies showing hydropic changes, predominance of low-frequency hearing loss, clinical efficacy of treatments targeted at inflammatory change/hydrops, and clinical efficacy of ablating the vestibular end-organ. SUMMARY: Although there is conflicting evidence regarding the cause and treatment of Ménière's disease, current evidence favors it as a disorder of the inner ear. Further research is needed to fully understand the mechanisms of Ménière's disease and how to improve diagnosis and treatment outcomes.

Infectious causes and mimickers of meniere's disease.

PURPOSE OF REVIEW: To review the evidence of a possible viral etiology of Meniere's disease, the role of antiviral therapy, as well as other infectious disease processes that may mimic Meniere's disease. Better understanding of the etiology of Meniere's disease and the role of various infectious disease processes may allow for more effective diagnosis and management. RECENT FINDINGS: There is evidence that viral infections - to Herpes simplex virus, cytomegalovirus, Epstein Barr virus, influenza, adenovirus, Coxsackie virus B, and Varicella Zoster Virus - may be involved in the development of Meniere's disease, however the evidence is inconsistent and the underlying mechanism remains theoretical. Nevertheless, antiviral therapy may be effective for a subset of patients with Meniere's disease. Lastly, other infectious diseases including Lyme disease and syphilis can present with symptoms similar to Meniere's disease. It is important to discern these from Meniere's disease to determine the appropriate treatment. SUMMARY: There is a paucity of high-quality evidence to support a viral etiology of Meniere's disease, and the current evidence appears circumstantial and inconsistent. Additional research is necessary to establish the mechanism and causative pathogens. Antiviral therapy may provide therapeutic benefit for a subset of patients with Meniere's disease. Furthermore, clinicians should be aware of other infectious mimics of Meniere's disease and include them in the differential diagnosis of patients presenting with Meniere's-like symptoms. Research on this subject continues to evolve, and data from these studies represent a growing repository of evidence that can be used to guide clinical decision-making.

Radiological feature heterogeneity supports etiological diversity among patient groups in Meniere's disease.

We aimed to determine the prevalence of radiological temporal bone features that in previous studies showed only a weak or an inconsistent association with the clinical diagnosis of Meniere's disease (MD), in two groups of MD patients (n = 71) with previously established distinct endolymphatic sac pathologies; i.e. the group MD-dg (ES degeneration) and the group MD-hp (ES hypoplasia). Delayed gadolinium-enhanced MRI and high-resolution CT data were used to determine and compare between and within (affected vs. non-affected side) groups geometric temporal bone features (lengths, widths, contours), air cell tract volume, height of the jugular bulb, sigmoid sinus width, and MRI signal intensity alterations of the ES. Temporal bone features with significant intergroup differences were the retrolabyrinthine bone thickness (1.04 ± 0.69 mm, MD-hp; 3.1 ± 1.9 mm, MD-dg; p < 0.0001); posterior contour tortuosity (mean arch-to-chord ratio 1.019 ± 0.013, MD-hp; 1.096 ± 0.038, MD-dg; p < 0.0001); and the pneumatized volume (1.37 [0.86] cm3, MD-hp; 5.25 [3.45] cm3, MD-dg; p = 0.03). Features with differences between the affected and non-affected sides within the MD-dg group were the sigmoid sinus width (6.5 ± 1.7 mm, affected; 7.6 ± 2.1 mm, non-affected; p = 0.04) and the MRI signal intensity of the endolymphatic sac (median signal intensity, affected vs. unaffected side, 0.59 [IQR 0.31-0.89]). Radiological temporal bone features known to be only weakly or inconsistently associated with the clinical diagnosis MD, are highly prevalent in either of two MD patient groups. These results support the existence of diverse-developmental and degenerative-disease etiologies manifesting with distinct radiological temporal bone abnormalities.

Is Inadequate Water Intake a Risk Factor for Vestibular Disorders?

BACKGROUND: Water is a vital nutrient for the human body system and failing to consume enough water could cause health problems. The purpose of this study is to investigate the relationship between water intake and vestibular system disorders. METHODS: Data from 93 patients (aged between 20 and 76 years) with vestibular disorders were analyzed in the study. The mean age of the patients was 46.96 ±13.94 years (female: 45.68 ±13.45, male: 49.96 ±14.85), and 69.9% (n=65) were female. Participants were sub-categorized into diagnostic groups as follows: benign paroxysmal positional vertigo, Meniere's disease, vestibular neuritis, vestibular migraine, and persistent postural perceptual dizziness. The water intake information was analyzed for total water, plain water, and caffeinated beverages separately and compared between groups. RESULTS: There was a significant difference between vestibular neuritis and benign paroxysmal positional vertigo (P < .001) and also between vestibular neuritis and Meniere's disease (P = .021) in terms of the intake values of plain water and total water. No significant difference was found between groups in caffeinated beverages intake (P = .151), and it was found that there is no statistically significant difference in plain water and total water intake in terms of gender (P > .05). CONCLUSION: The most significant result of this study is that inadequate water intake can be a risk factor for some forms of peripheral vestibular disorders. People should be informed about the importance of drinking water and be encouraged to increase their water intake.

Bidirectional Transport of IgE by CD23 in the Inner Ear of Patients with Meniere's Disease.

Meniere's disease (MD) is a disorder of the inner ear characterized by episodes of spontaneous vertigo, fluctuating hearing loss, and tinnitus. Recent studies have demonstrated that IgE may play a role in the pathogenesis of MD. Patients with MD (n = 103), acoustic neuroma (n = 5), and healthy subjects (n = 72) were recruited into the study. Serum from the participants was analyzed for IgE and type 2-related cytokines. IgE and CD23 expression levels in vestibular end organs of patients, C57BL/6 mice, or mouse HEI-OC1 cells were analyzed. Finally, the role of CD23 in IgE transcytosis was assessed using HEI-OC1 cells. Serum IgE was elevated in patients with MD and positively correlated with clinical symptoms. IL-4, IL-5, IL-10, IL-13, and CD23 levels were increased in patients with MD compared with the control group. In the transcytosis assay, mouse IgE was found to be bidirectionally transported across the HEI-OC1 cell monolayer. Additionally, CD23 downregulation using a small interfering RNA approach significantly reduced the efficiency of IgE transcytosis, suggesting that IgE is transported by CD23. Furthermore, exposure to IL-4 increased CD23 expression and enhanced IgE transcytosis in the HEI-OC1 cells and primary vestibular end organs. Our study indicated that IgE may play a role in the pathophysiology of MD. In addition, CD23-mediated IgE transcytosis in the hair cells may play a critical role in initiating inflammation in the inner ear. Thus, reducing the level of IgE may be a potentially effective approach for MD treatment.

Retrosigmoid Vestibular Neurectomy for Meniere Disease: A Technical Note.

BACKGROUND: Meniere disease (MD) is an idiopathic peripheral pathology involving the acoustic apparatus. One of the most critical challenges in managing MD is intractable vertigo. In this context, retrosigmoid vestibular neurectomy has been described as a safe and effective technique to manage this symptom when it is resistant to first- and second-line treatments. This article analyzed the alternative treatment options, specific surgical anatomy, and relevant details of vestibular neurectomies performed for intractable MD. METHODS: Relevant neurovascular landmarks, critical surgical steps, adequate indications, and potential pitfalls of retrosigmoid vestibular neurectomy were analyzed based on an illustrative clinical case of intractable MD. RESULTS: The illustrative case demonstrated how early recognition of the facial nerve and the vestibulocochlear plane is fundamental to performing retrosigmoid vestibular neurectomy. This procedure is indicated in cases of resistant MD with preoperative hearing integrity. Potential pitfalls of this technique are incomplete neurotomy, nerve regeneration, comorbidities in the contralateral ear, adverse anatomy, the possibility of nonotologic vertigo, and incomplete vestibular compensation. CONCLUSIONS: Vestibular neurectomy represents a safe and effective technique to manage MD that is resistant to medical treatment, allowing symptom control and hearing preservation. Nevertheless, detailed knowledge of surgical anatomy and possible pitfalls is of paramount importance to achieve a good outcome.

Effects of short- and long-term exposure to air pollution and meteorological factors on Meniere's disease.

The association between air pollutants and Meniere's disease has not been explored. The present study investigated the relationship between meteorological factors and air pollutants on Meniere's disease. Participants, aged ≥ 40 years, of the Korean National Health Insurance Service-Health Screening Cohort were included in this study. The 7725 patients with Meniere's disease were matched with 30,900 control participants. The moving average meteorological and air pollution data of the previous 7 days, 1 month, 3 months, and 6 months before the onset of Meniere's disease were compared between the Meniere's disease and control groups using conditional logistic regression analyses. Additional analyses were conducted according to age, sex, income, and residential area. Temperature range; ambient atmospheric pressure; sunshine duration; and levels of SO2, NO2, O3, CO, and PM10 for 1 month and 6 months were associated with Meniere's disease. Adjusted ORs (odds ratios with 95% confidence interval [CI]) for 1 and 6 months of O3 concentration were 1.29 (95% CI 1.23-1.35) and 1.31 (95% CI 1.22-1.42), respectively; that for the 1 and 6 months of CO concentration were 3.34 (95% CI 2.39-4.68) and 4.19 (95% CI 2.79-6.30), respectively. Subgroup analyses indicated a steady relationship of O3 and CO concentrations with Meniere's disease. Meteorological factors and air pollutants were associated with the rate of Meniere's disease. In particular, CO and O3 concentrations were positively related to the occurrence of Meniere's disease.

Association between Meniere's disease and air pollution in South Korea.

Meniere's disease is thought to be a disorder of the inner ear function, affected by genetic and environmental factors. Several recent studies have shown that air pollution could affect middle and inner ear diseases. The purpose of this study was to investigate the relationship between the Meniere's disease occurrence and air pollution status in Korea. This study used a time-stratified case-crossover design. Hospital visit data by Meniere's disease were collected from the Korea National Health Insurance Service-National Sample Cohort (NHIS-NSC) database. Daily air pollution data for sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and particulate matter (PM10: ≤ 10 µm in diameter, and PM2.5: ≤ 2.5 µm in diameter) were collected from the National Ambient air quality Monitoring Information System (NAMIS) database. We used two-stage analysis to assess the association between degree of air pollution and the occurrence of Meniere's disease. In the first stage, region-specific analysis was conducted to estimate the odds ratios (ORs) of Meniere's disease risk associated with each air pollutant exposure by using conditional logistic regression for matched case-control sets in 16 regions. In the second stage, region-specific ORs from the first stage were combined and the pooled effect estimates were derived through fixed and random effect meta-analysis. Subgroup analysis was conducted for age, sex, seasonality, and urbanization of residence. In total, 29,646 (32.1% males and 67.9% females) Meniere's disease cases were identified from Korea NHIS-NSC database between 2008 and 2015. Overall, SO2, NO2, CO, and PM10 showed significant correlation with Meniere's disease risk at immediate lags, and weaker correlation at delayed lags, whereas O3 showed slightly negative correlation at the immediate lag (lag0) and PM2.5 did not show strong correlation (SO2: 1.04 [95% confidence interval: 1.01, 1.06]; NO2: 1.08 [1.06, 1.11]; CO: 1.04 [1.02, 1.06]; O3: 0.96 [0.93, 0.99]: statistically significant ORs at lag0 are listed). These positive and negative associations between Meniere's disease and each air pollutant were generally stronger in the age of 40-64, female, summer (June-August) season, and urban subgroups. Our results showed that hospital visits for Meniere's disease were associated with the measured concentrations of ambient air pollutants SO2, NO2, CO, and PM10. Further studies are required to confirm these associations and find their mechanisms.

Cerebellopontine Angle and Internal Auditory Canal Lipomas: Case Series and Systematic Review.

OBJECTIVES/HYPOTHESIS: Cerebellopontine angle (CPA) and internal auditory canal (IAC) lipomas are rare, benign tumors comprising 0.08% of all intracranial tumors and can be mistaken for other, more common lesions of the CPA/IAC such as vestibular schwannoma. The purpose of this study was to review the literature and assess the evolution of CPA/IAC lipoma diagnosis and management. In addition, we present 17 new lipomas, matching the largest known case series of this rare tumor. STUDY DESIGN: Retrospective case series and systematic review. METHODS: Systematic review of the literature was performed using PubMed and Google Scholar. References from identified articles were also reviewed to identify potential additional manuscripts. Manuscripts and abstracts were reviewed to identify unique cases. For the case series, the charts of all CPA/IAC lipoma patients seen at a single institution from 2006-2019 were manually reviewed. Logistic regression and chi-squared analysis were performed where appropriate. RESULTS: A total of 219 unique lipomas have been reported in the literature, including 17 presented in this study. Surgical management has been performed in 46% of cases and has been conducted less often in recent decades, likely due to improved radiographic diagnostic capabilities and understanding of surgical outcomes. Surgical management is associated with worse neurologic outcomes (P = .002) and has become less common in recent decades. Although growth is unlikely, it has been demonstrated in patients into their 30s. CONCLUSIONS: Accurate radiographic diagnosis is imperative for appropriate patient management, as CPA/IAC lipomas should typically be managed through observation and serial imaging whereas vestibular schwannomas and other CPA/IAC lesions may require microsurgical or radiosurgical intervention depending on growth and symptomatology. Laryngoscope, 131:2081-2087, 2021.

High level of IgE in acute low-tone sensorineural hearing loss: A predictor for recurrence and Meniere Disease transformation.

BACKGROUND: Autoimmunity may play an important role in sudden onset sensorineural hearing loss. However, little is known about the relationship between immunoglobulin E (IgE) and acute low-tone sensorinerual hearing loss (ALHL). OBJECTIVES: To investigate the relationship between IgE level and endolymphatic hydrops and outcomes of ALHL. METHODS: A total of 242 subjects with sudden onset hearing loss, including 115 with ALHL and 127 with idiopathic sudden sensorineural hearing loss (ISSHL), were included in this study. Peripheral venous blood samples of 242 subjects were collected for detection. Clinical data, IgE level, and distribution of allergens were compared between the ALHL and ISSHL groups. The ALHL group received an electrocochleogram (ECochG) test and a follow-up in the outpatient unit or by telephone to evaluate outcomes. RESULTS: Compared to the values in the ISSHL group, a significantly younger onset age (42.30±14.33 years old), higher female onset proportion (72/115, 62.61%), increased total IgE level (median: 66.47, interquartile range: 24.56, 180.96, IU/mL) and specific IgE level (median: 9.42, interquartile range: 1.42, 22.23 IU/mL) were noted in the ALHL group. A clear difference in allergen distribution was noted between the ALHL and ISSHL groups (p=.001). Total IgE and specific IgE levels were factors that contributed to the SP/AP ratio in the electrocochleogram (ECochG) (R2=0.413) in ALHL group. Finally, during the follow-up (17.61±3.46 months) for the ALHL group, 37 subjects recurred, and 17 subjects developed Meniere Disease. In the ROC curve for ALHL recurrence, the area under the curve (AUC) of total IgE was 0.709 and that of specific IgE was 0.679. For MD transformation, the AUC of total IgE was 0.736 and that of specific IgE was 0.716. CONCLUSIONS: High IgE levels correlated with an enhanced SP/AP ratio in ALHL. High IgE levels could be used as a predictor of ALHL recurrence and MD transformation.

Incidence of Developing Contralateral Ménière's Disease in Patients Undergoing Transmastoid Labyrinthectomy for Unilateral Ménière's Disease.

OBJECTIVES: To analyze the incidence of developing contralateral Ménière's disease (MD) in patients who undergo labyrinthectomy for vestibular dysfunction in unilateral MD. STUDY DESIGN: Retrospective chart review. PARTICIPANTS AND METHODS: Adult patients with a diagnosis of MD who underwent surgical labyrinthectomy with minimum follow-up of 12 months were included. Patients who experienced chemical labyrinthectomy, surgical labyrinthectomy for a diagnosis other than MD, contralateral ear surgery, or bilateral MD before the labyrinthectomy were excluded. The key outcome measure is whether symptoms of MD developed in the contralateral ear post-labyrinthectomy. Statistical analysis was performed using χ2 (Fisher exact) test for discrete variables and the Student t test for continuous variables. A P value < .05 was considered significant. RESULTS: Of the140 patients who underwent labyrinthectomy for intractable vertigo due to unilateral MD, 84 had at least 1 year follow-up appointments. Twelve percent (10/84) of these patients developed contralateral MD, which was diagnosed by a neuro-otologist based on symptoms consistent with MD, including low-frequency sensorineural hearing loss. Average age in years is 63.12 (10.83; mean [SD]) at time of surgery. Average follow-up was 35.57 (15.89) months (range: 12-69 months). CONCLUSION: The incidence of contralateral MD development in patients who underwent labyrinthectomy for unilateral MD is 12%. The current literature states that MD has a 30% bilateral involvement rate. Our incidence is significantly lower when compared to the current literature.

Menière's disease caused by CGRP - A new hypothesis explaining etiology and pathophysiology. Redirecting Menière's syndrome to Menière's disease.

This paper provides a new hypothetical explanation for the etiopathology and pathophysiology of Menière's Disease (MD), which to date remain unexplained, or incompletely understood. The suggested hypothesis will explain the close connection of MD and Migraine, the coexistence of endolymphatic hydrops (ELH) and Menière attacks and the signs of inflammation detected in the inner ears of MD patients. Although as yet unproven, the explanations provided appear highly plausible and could pave the way for the generation of the first animal model of MD - an invaluable asset for developing new treatment strategies. Furthermore, if proven correct, this hypothesis could redefine and also reset the actual name of Menière's Syndrome to Menière's Disease.

Live imaging and functional changes of the inner ear in an animal model of Meniere's disease.

The symptoms of Meniere's disease (MD) are generally considered to be related to endolymphatic hydrops (EH). There are many recent reports supporting the possibility that vasopressin (VP) is closely linked to the formation of EH in Meniere's disease. Based on this, we developed a clinically relevant animal model of Meniere's disease in which a VP type 2 receptor agonist was administered after electrocauterization of the endolymphatic sac. We report live imaging of the internal structure, and functional changes of the inner ear after electrocauterization of the endolymphatic sac and administration of a VP type 2 receptor agonist. In this model, the development of EH was visualized in vivo using optical coherence tomography, there was no rupture of Reissner's membrane, and low-tone hearing loss and vertiginous attacks were observed. This study suggested that acute attacks are caused by the abrupt development of EH. This is the first report of live imaging of the development of EH induced by the administration of a VP type 2 receptor agonist.

Current Understanding and Clinical Management of Meniere's Disease: A Systematic Review.

Meniere's disease (MD) is a set of uncommon disorders with core phenotype of tinnitus, episodic vertigo, and sensorineural hearing loss. MD shows a genetic predisposition and a family history is found in 10% cases, with an autosomal dominant inheritance pattern. It is a multifactorial condition whose onset and development are triggered by the combined effect of genetic and environmental factors. Histopathological studies have associated MD with the accumulation of endolymph in the cochlea and the vestibular organs. However, endolymphatic hydrops does not fully explain the persistence of tinnitus, hearing loss progression, or the frequency of vertigo attacks.There are several comorbidities associated with MD, such as migraine, anxiety, autoimmune, and autoinflammatory disorders, adding more complexity to the phenotype. This "extended phenotype" can make the diagnosis and clinical management more complex, but it could also lead to a better characterization, understanding, and treatment of MD patients.We have conducted a systematic review on MD to update current knowledge, focusing on its mechanisms, diagnosis, comorbidities, and practical management.

[A role of vascular risk factors in the development of peripheral vestibulopathy]. / Rol' faktorov serdechno-sosudistogo riska v razvitii perifericheskikh vestibulopatii.

The development of peripheral vestibular disorders are often thought to be associated with vascular mechanisms, taking into account terminal type of inner ear blood supply and other predisposing factors. A number of studies indicates a high frequency of vascular risk factors in the patients with vestibular neuronitis and benign paroxysmal positional vertigo (BPPV). According to other results, migraine is widely spread among patients with Meniere's disease and BPPV. However currently there is no evidence for casual relationship between vascular factors and development of peripheral vestibulopathy. The only exclusion is labyrinthine infarction, which develops as a result of posterior circulation disorder. More research is needed in this area.

Are viral-infections associated with Ménière's Disease? A systematic review and meta-analysis of molecular-markers of viral-infection in case-controlled observational studies of MD.

Despite considerable research, it remains controversial as to whether viral-infections are associated with Meniere's Disease (MD), a clinically heterogeneous set of chronic inner-ear disorders strongly associated with endolymphatic hydrops. Here, we investigated whether viral-infections are associated with MD through a systematic review and meta-analysis of observational clinical studies using molecular-diagnostics. Eligible for inclusion were case-controlled studies which ascertained molecular-determinants of past or present viral-infection through either viral nucleic acids or host serological marker in MD cases and non-MD controls. Across online databases and grey literature, we identified 210 potentially relevant articles in the English language, from which a total of 14 articles fully satisfied our eligibility criteria such that meta-groups of 611 MD-cases and 373 controls resulted. The aggregate quality of the modest-sized (14 studies) body of evidence was limited and varied considerably with regards to participant selection, matching, and ascertainment(s) and determinant(s) of viral-infection. Most data identified concerned the human cytomegalovirus (CMV), and meta-analysis of eligible studies revealed that evidence of CMV-infection was associated approximately three-fold with MD compared to controls, however the timing of the infections was indeterminate as the pooled analyses combined antiviral serological markers with viral nucleic acid markers. No association was found for any of HSV-1, -2, VZV, or EBV. Associative analyses of any viral species not aforementioned were precluded by limited data, and thus potential associations between other viral species and MD, especially other than Herpesviridae, are yet to be characterised. Overall, we have found a small association between CMV-infection and MD, however it is to be determined for what sub-groups of MD this finding may be relevant, and ideally the reported association remains would be reproduced by a greater volume of higher quality evidence.

Solute carrier family 4 member 1 might participate in the pathogenesis of Meniere's disease in a murine endolymphatic hydrop model.

Background: To date, the pathogenesis of Meniere's disease (MD) remains unclear. Previous research found that the SLC4A1 gene significantly down-regulated. Aims: This study sought to understand the effect of SLC4A1 on the pathogenesis of MD. ELH C57 mice models were induced by intraperitoneal injection of AVP. Material and methods: The mRNA expression levels of SLC4A1, SLC4A10 and SLC26A4 were monitored by real-time quantitative PCR, the protein expression levels of SLC4A1 were monitored by immunoblotting and immunofluorescence before and after the ELH. DIDS is an inhibitor of SLC4A1. The expression levels of SLC4A1 were also monitored in the AVP + DIDS group. Results: We successfully established the model of ELH after applied AVP. The results of HE staining showed displacement of Reissner's membrane with bulge to scala vestibule in ears of the AVP group. Cochlea/ELS SLC4A1 protein and SLC4A1, SLC4A10, SLC26A4 mRNA expressions were reduced significantly in C57 mice of the AVP group. The SLC4A1 protein expression levels and SLC4A1, SLC4A10, SLC26A4 mRNA expression levels declined more obvious in the cochlea and ELS in C57 mice of the AVP + DIDS group. Conclusions and significance: SLC4A1 was a protective factor in the pathogenesis of MD, but the mechanisms were unknown.