Recent Advancements in the Regeneration of Auditory Hair Cells and Hearing Restoration

Abstract

Neurosensory responses of hearing and balance are mediated by receptors in specialized neuroepithelial sensory cells. Any disruption of the biochemical and molecular pathways that facilitate these responses can result in severe deficits, including hearing loss and vestibular dysfunction. Hearing is affected by both environmental and genetic factors, with impairment of auditory function being the most common neurosensory disorder affecting 1 in 500 newborns, as well as having an impact on the majority of elderly population. Damage to auditory sensory cells is not reversible, and if sufficient damage and cell death have taken place, the resultant deficit may lead to permanent deafness. Cochlear implants are considered to be one of the most successful and consistent treatments for deaf patients, but only offer limited recovery at the expense of loss of residual hearing. Recently there has been an increased interest in the auditory research community to explore the regeneration of mammalian auditory hair cells and restoration of their function. In this review article, we examine a variety of recent therapies, including genetic, stem cell and molecular therapies as well as discussing progress being made in genome editing strategies as applied to the restoration of hearing function.

2,3,4′,5-Tetrahydroxystilbene-2-O-β-D-Glucoside (THSG) Activates the Nrf2 Antioxidant Pathway and Attenuates Oxidative Stress-Induced Cell Death in Mouse Cochlear UB/OC-2 Cells

“…Hearing loss is a serious global morbidity that affects 360 million people worldwide [1], and this neurological disability impacts both the physical and mental health of patients [2]. Recent research has revealed several mechanisms and molecules that contribute to hearing loss, such as oxidative stress and apoptotic cell death [3].…”

Salt-Inducible Kinase 3 Haplotypes Associated with Noise-Induced Hearing Loss in Chinese Workers

“…The organ of Corti is a sensory structure that detects sound in mammals possessing dual sensory systems with inner and outer hair cells which are important to hearing ability [Lim, 1986]. Noise exposure may cause harm to the organ of Corti resulting in irreversible structural cellular damage to the hair cells and supporting cells [Mittal et al, 2017;Moser and Starr, 2016]. SIK3 is important during the early stages of development in hair cells or stereocilia, and a maintenance function of SIK3 in spiral ganglion was found in mice [Wolber et al, 2014].…”

Advances in understanding of presbycusis

“…Animal studies suggest that IGF1 promotes inner ear neuronal development by supporting neurogenesis, differentiation and proliferation of neuronal progenitor cells (Aburto, Magarinos, Leon, Varela‐Nieto, & Sanchez‐Calderon, ; Ayaso, Nolan, & Byrnes, ; Varela‐Nieto, Murillo‐Cuesta, Rosa, Lassatetta, & Contreras, ; Tafra et al, ). IGF1 may also promote cochlear hair cell survival by limiting the degree of cochlear inflammation and oxidative stress and down‐regulating pro‐apoptotic gene expression (Mittal et al, ; Yamahara et al, ; Yang et al, ).…”

“…Expression of IGF1 is highest during late cochlear development, declines significantly after birth; although IGF‐1 expression is maintained throughout life, circulating bioactive IGF‐1 levels decline with age, leading to increased inflammation and failure of intracellular renewal mechanisms (Mittal et al, ; Murillo‐Cuesta, Rodríguez‐de la Rosa, Cediel, Lassaletta, & Varela‐Nieto, ; Vestergaard et al, ). IGF1 has been detected throughout the mouse inner ear, including the spiral ganglion, spiral ligament, stria vascularis, hair cells, and in vestibular tissues (de la Rosa et al, ; Degerman et al, ; Riva, Donadieu, Magnan, & Lavieille, ).…”