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Review
. 2024 May 13;13(5):598.
doi: 10.3390/antiox13050598.

A Consolidated Understanding of the Contribution of Redox Dysregulation in the Development of Hearing Impairment

Xin Yi Yeo  1   2 , Soohyun Kwon  2   3 , Kimberley R Rinai  4 , Sungsu Lee  5 , Sangyong Jung  2 , Raekil Park  6
Affiliations
Review

A Consolidated Understanding of the Contribution of Redox Dysregulation in the Development of Hearing Impairment

Xin Yi Yeo et al. Antioxidants (Basel). .

Abstract

The etiology of hearing impairment is multifactorial, with contributions from both genetic and environmental factors. Although genetic studies have yielded valuable insights into the development and function of the auditory system, the contribution of gene products and their interaction with alternate environmental factors for the maintenance and development of auditory function requires further elaboration. In this review, we provide an overview of the current knowledge on the role of redox dysregulation as the converging factor between genetic and environmental factor-dependent development of hearing loss, with a focus on understanding the interaction of oxidative stress with the physical components of the peripheral auditory system in auditory disfunction. The potential involvement of molecular factors linked to auditory function in driving redox imbalance is an important promoter of the development of hearing loss over time.

Keywords: auditory deficit; cochlea function; hearing loss; oxidative stress; redox imbalance.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The anatomical and biological structure of the auditory system. (A) The anatomy of the auditory system comprises the outer auditory canal (outer ear), auditory ossicles (middle ear), and the cochlea (inner ear). (B) The outer ear canal forms a physical passageway which collects and channels external sound signals into the middle ear. (C) The sound waves are made up of high-amplitude vibrations of air particles (represented by a black waveform with an arrow showing the direction of movement) which displace the eardrum from its basal position (top compared with bottom figure, red box). The physical connection between the eardrum, ossicles, and tympanic membrane allows physical conduction of the movement of the eardrum to the tympanic membrane and the inner ear of the auditory system. (D) The inner ear is made up of the fluid-filled, spiral-shaped cochlea, which contains the mechanosensory hair cells required for the transduction of auditory signals into the CNS (top left). The stereocilia on hair cells are connected to the tectorial membrane through the calcium-rich filamentous structures that allow the transmission of fluid-dependent movement of the tectorial membrane to the mechanosensitive mechanoelectrical transduction (MET) channel of the hair cells. Activation of the sensory hair cells leads to the release of neurotransmitters targeting the innervating auditory nerve for transmission of auditory signals into the CNS (top right). The inner and outer hair cells comprise slightly different molecular components, which allow their specialized functions (bottom).
Figure 2
Figure 2
The structural and functional impact of hereditary mutations in genes involved in auditory function. Myosin VI (Myo6) and alpha-tectorin (TECTA) are involved in stereocilia structure maintenance. Mutations in Myo6 and TECTA lead to the mislocalization of the actin (MYO, bottom right) and the loss in alignment of the stereocilia structure to the tectorial membrane (TECTA, bottom right). Alternatively, mutations in the functional components of the hair cells can lead to significant alteration of the ionic gradient required for maintenance of the endolymphatic potential (GJB, right) and hair cell membrane potential (KCNQ4, right), which impacts the ease of hair cell activation and signal transmission to the auditory nerve. OTOF and SLC17A8 mutations are linked to a reduction in the quantal size of the neurotransmitter released (SLC17A8, right) and loss of the abilities of vesicle fusion and neurotransmitter release (OTOF, bottom right) upon IHC activation. Changes to the OHC electromobility (SLC26A5, depolarization and hyperpolarization) further reduce the sensitivity of the sensory hair cells toward stimulus-evoked activation. The contributions of individual effects or the combinatorial effect of the altered structural and functional components reduce the sensitivity and, in severe cases, ablate stimulus-dependent hair cell activation, leading to hearing impairment.
Figure 3
Figure 3
Progressive loss of cells and auditory function with time. Genetic predisposition to auditory disfunction and cumulative exposure toward ototoxic stimulus leads to the gradual loss of sensory hair cells over time.
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