2020年 · 第03卷第02期

Myosins comprise a large superfamily of adenosine triphosphatases (ATPases) that interact with actin filaments to generate motility or force. Unconventional myosins are implicated in diverse cellular processes including organelle trafficking, F-actin organization and cell movement. The unconventional myosin, myosin XVA (MYO15A), is localized at the tips of stereocilia in the inner ear hair cells and plays important roles in the development and maintenance of stereocilia. Mutations in MYO15A/Myo15a genes are responsible for hearing loss DFNB3 and shaker-2 in human and mice, respectively. In the present review, we will discuss the expression and alternative splicing of the MYO15A gene, the biochemical properties of the MYO15A protein and the association of MYO15A mutations with hearing loss. We will also discuss the recent investigations into the mechanism of how MYO15A regulates stereocilia development and maintenance. At present we are just beginning to appreciate the important roles of MYO15A in stereocilia, and further investigations are warranted to fully understand them.

The development of applications for the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) system has increased greatly in recent years, especially in the area of gene therapy by efficient in vivo genome editing. Although great success has been achieved in repairing and rewriting genomes through homology-directed repair coupled with Cas9 nuclease cleavage, its in vivo efficiency is insufficient for gene therapy. Base editing is a next-generation genome-editing tool that does not involve double-stranded DNA breaks and uses components of the CRISPR system together with other enzymes to make point mutations directly in cellular DNA or RNA. Base editors, composed of an engineered deaminase and a catalytically impaired CRISPR/Cas9 variant, are powerful tools for targeted base editing in cells and organisms. In non-dividing cells, base editors can directly transform one base or base pair into another, efficiently installing a point mutation. Undesired by-products of editing are seldom generated during this procedure. Herein we review the different base-editing platforms, including their deaminase recruitment strategies and editing outcomes, and the in vivo delivery of base editors. Additionally, we summarize therapeutic applications of base editing in disorders of the inner ear.

Many factors can cause inner ear injury, such as noise exposure, chemicals, viral infection, and radiation. The main pathological manifestations of inner ear injury are local hypoxia-ischemia, micro-trauma, and an increased level of reactive oxygen species and inflammatory mediators. The contribution of the inflammatory response to the mediation of cochlear and vestibular pathologies has received increasing attention in recent years. Aseptic inflammation can devastate audition and balance, which can lead to many typical clinical inner ear diseases. In this review, we will discuss the most pertinent and recent research on inflammatory mechanisms in inner ear injury. We will also discuss the pathophysiology of some common and significant ear diseases, such as sudden sensorineural hearing loss, age-related hearing loss, noise-induced hearing loss, and Meniere’s disease.

Benign paroxysmal positional vertigo (BPPV) is the most common vestibular peripheral disease, and has increasingly become the focus of research on vertigo diseases in recent years. In particular, otolaryngology and neurology societies worldwide have placed a greater focus on the study of BPPV. This article reviews the current diagnosis and treatment status and research progress of benign paroxysmal positional vertigo in China from the aspects of disease etiology, pathology, and pathophysiology. We will also consider potential future research in this field.