Toru Miwa

Although numerous causative genes for hereditary hearing loss have been identified, there are no fundamental treatments for this condition. Herein, we describe a novel potential treatment for genetic hearing loss. Because mutations or deletions in the connexin (Cx) genes are common causes of profound congenital hearing loss in both humans and mice, we investigated whether gene supplementation therapy using the wild-type Cx gene could cure hearing loss. We first generated inner ear-specific conne

Batch culture experiments showed that permeabilized cells and membranes of Ruminococcus albus and Fibrobacter succinogenes, acid-intolerant celluloytic bacteria, have only one-fourth to one-fifth as much H(+)-ATPase as Megasphaera elsdenii and Streptococcus bovis, which are relatively acid tolerant. Even in the cells grown in continuous culture at pH 7.0, the acid-intolerant bacteria contained less than half as much H(+)-ATPase as the acid-tolerant bacteria. The amounts of H(+)-ATPase in the aci

Tsukushi (TSK)-a small, secreted, leucine-rich-repeat proteoglycan-interacts with and regulates essential cellular signaling cascades. However, its functions in the mouse inner ear are unknown. In this study, measurement of auditory brainstem responses, fluorescence microscopy, and scanning electron microscopy revealed that TSK deficiency in mice resulted in the formation of abnormal stereocilia in the inner hair cells and hearing loss but not in the loss of these cells. TSK accumulated in nonpr

The Dach1 gene is expressed in the inner ear of normal mouse embryos in the area that differentiates into the cochlear stria vascularis (SV). We hypothesized that Dach1 downregulation in the inner ear would lead to SV dysplasia. However, because Dach1 knockout is embryonic lethal in mice, the role of Dach1 in the inner ear is unclear. , Here, we established inner ear-specific Dach1-knockdown mice and showed that Dach1 downregulation resulted in hearing loss, reduced endocochlear potential, and s

Macrophages play important roles in tissue homeostasis and inflammation. Recent studies have revealed that macrophages are dispersed in the inner ear and may play essential roles in eliciting an immune response. Autoinflammatory diseases comprise a family of immune-mediated diseases, some of which involve sensorineural hearing loss, indicating that similar mechanisms may underlie the pathogenesis of immune-mediated hearing loss. Autoimmune inner ear disease (AIED) is an idiopathic disorder chara

Age-related hearing loss (ARHL) is the most common form of hearing loss and the predominant neurodegenerative disease associated with aging. <i>Sirtuin 1 (SIRT1)</i> is associated with the most complex physiological processes, including metabolism, cancer onset, and aging. SIRT1 protein levels are enhanced by the conversion of nicotinamide to N¹-methylnicotinamide (MNAM), independent of its mRNA levels. Moreover, MNAM has implications in increased longevity achieved through its mitoho

This study aimed to examine the types and causes of dizziness experienced by individuals after a major earthquake. This cross-sectional study enrolled healthy participants who experienced the 2016 Kumamoto earthquakes and their aftershocks. Participants completed a questionnaire survey on their symptoms and experiences after the earthquakes. The primary outcome was the occurrence of dizziness and the secondary outcome was the presence of autonomic dysfunction and anxiety. Among 4,231 eligible pa

The mouse otocyst, an anlage of the inner ear, is an attractive experimental target for developing treatment modalities for congenital inner ear diseases and for studying inner ear development. Poly-arginine (6-12 residues) is a cell-penetrating peptide and can be used to deliver cargo into cells. Here, we achieved transutero delivery of enhanced green fluorescent protein (EGFP) fused to a nine-arginine peptide into mouse embryonic otocysts. The EGFP signal was detected both in the lining cells

Mitochondrial dysfunction is associated with aging and age-related hearing loss (AHL). However, the precise mechanisms underlying the pathophysiology of hearing loss remain unclear. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) enables efficient intramitochondrial translation by catalyzing the deposition of 2-methylthio modifications on mitochondrial tRNAs. Here we investigated the effect of defective mitochondrial protein translation on hearing and AHL in a Cdk5rap1 deficiency C57BL/6

This retrospective chart review aimed to examine both the vestibular function and causes of dizziness experienced by individuals following a series of major earthquakes and repetitive aftershocks. All patients with balance disorders who experienced the 2016 Kumamoto earthquakes and their aftershocks completed questionnaires relevant to balance disorders and were enrolled in this study after providing informed consent. There were 2.8 times more patients with balance disorders post the earthquake.

These findings in SS patients suggest that saccule-inferior vestibular function is maintained at early stages of the disorder. Our study may help to clarify the mechanism of SS.