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Genes and Hearing Loss: Relationship to Oxidative Stress and Free Radical Formation

  • Chapter
Free Radicals in ENT Pathology

Abstract

Genetic evidence in humans and in mice supports the significance of reduction–oxidation (redox) balance in the development and maintenance of normal hearing. Variants in genes that directly or indirectly alter redox balance result in increased susceptibility to hearing loss, including age-related hearing loss and loss associated with noise and ototoxic drugs. Preexposure to low levels of noise, heat, or drugs activates pathways, including oxidative stress response genes, that can protect the cochlea from subsequent ototoxic damage. Further insight into the genetic control of redox balance and its influence on hearing will be accelerated by a variety of advances in genetic and genomic approaches. These include more extensive genome-wide association analyses and next-generation sequencing in human populations to identify genetic variants associated with age- and ototoxin-related hearing loss. In addition, innovations in cellular reprogramming strategies and genome engineering techniques will broaden the range of genetic model systems in which to investigate mechanisms of cochlear pathology and to test therapeutic interventions.

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Abbreviations

ARHL:

Age-related hearing loss

CAT :

Catalase

CR:

Caloric restriction

CRISPR/Cas:

Clustered regularly interspaced short palindromic repeat/Cas9 endonucleases

ER:

Endoplasmic reticulum

ES:

Embryonic stem

GWAS:

Genome-wide association studies

H2O2 :

Hydrogen peroxide

HPA:

Hypothalamic–pituitary–adrenal axis

HSFs:

Heat shock transcription factors

HSPs:

Heat shock proteins

IDH2 :

Mitochondrial isocitrate dehydrogenase 2

Mt-Tr :

Mitochondrial tRNA arginine gene

NAT2 :

N-Acetyltransferase 2 gene

NF-κb:

Nuclear factor kappaB

NGS:

Next-generation sequencing

NIHL:

Noise-induced hearing loss

Redox:

Reduction–oxidation

ROS:

Reactive oxygen species

Sirt :

Sirtuin

SNPs:

Single nucleotide polymorphisms

SOD:

Superoxide dismutase

TALENs:

Transcription activator-like effector nucleases

UPR:

Unfolded protein response

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Authors and Affiliations

  1. University of Michigan, 1150 W. Medical Center Drive, 9301D MSRB III, Ann Arbor, MI, 48109, USA

    David Kohrman Ph.D.

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  1. David Kohrman Ph.D.
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Correspondence to David Kohrman Ph.D. .

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Editors and Affiliations

  1. Cochlear Signaling & Tissue Engin., University of Michigan Kresge Hearing Research Institute, Ann Arbor, Michigan, USA

    Josef Miller

  2. Dept of Speech , Lang & Hearing Sci, Univ of Florida Health Sciences Center, Gainesville, Florida, USA

    Colleen G. Le Prell

  3. Div . of Otolaryngology Head & Neck Surgery, SIU School of Medicine, Springfield, Illinois, USA

    Leonard Rybak

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Kohrman, D. (2015). Genes and Hearing Loss: Relationship to Oxidative Stress and Free Radical Formation. In: Miller, J., Le Prell, C., Rybak, L. (eds) Free Radicals in ENT Pathology. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Cham. https://doi.org/10.1007/978-3-319-13473-4_17

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