Hearing loss and tinnitus: association studies for complex-hearing disorders in mouse and man

Boussaty, Ely Cheikh; Friedman, Rick A.; Program, Million Veteran; Clifford, Royce E

doi:10.1007/s00439-021-02317-9

Cited by 6 publications

(4 citation statements)

References 92 publications

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“…These molecular signatures serve as signposts from which the field can use to orient itself for further targeted experimental approaches. The identification of these specific targets is a prerequisite before the development of genetic intervention and treatment, making the efforts embarking on these studies extremely important [31]. GWASs are based off large datasets from self-reported tinnitus and have been instrumental for identifying significant variants and have taken many forms throughout the brief history of tinnitus genetics research.…”

Section: Genetics Studies Begin To Unravel a Genetic Architecture For...mentioning

confidence: 99%

The Road Traveled and Journey Ahead for the Genetics and Genomics of Tinnitus

Vona

2022

Mol Diagn Ther

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The feasibility to unravel genetic and genomic signatures for disorders affecting the auditory system has accelerated since arriving in the post-genomics era roughly 20 years ago. Newly emerging studies have provided initial landmarks signaling heritability and thus, a genetic link, to severe tinnitus. Tinnitus, the phantom perception of ringing in the ears, is experienced by at least 15% of the adult population and can be extremely disabling. Despite its ubiquity, there is no cure for tinnitus and modalities offering relief are often of limited success. Because tinnitus is frequently reported in patients with acquired conductive or sensorineural hearing impairment, it has been widely accepted that tinnitus is secondary to and a symptom arising from hearing impairment. However, tinnitus has also been identified in the absence of auditory dysfunction and in young individuals, resulting in a debate about its origins. Genetics studies have identified severe tinnitus as a complex disorder arising from gene and environment interactions, refining its classification as a neurological disorder and, in at least a subset of patients, it appears not as a symptom of another health issue. This current opinion summarizes several recent studies that have challenged a long-accepted dogma and postulates how this information could eventually be used in the future to help patients. It is with great hope that this knowledge opens translational paths to provide relief for the many who suffer from the burden of tinnitus on a daily basis.

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Section: Genetics Studies Begin To Unravel a Genetic Architecture For...mentioning

confidence: 99%

The Road Traveled and Journey Ahead for the Genetics and Genomics of Tinnitus

Vona

2022

Mol Diagn Ther

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“…Although hearing loss can target different cell types within the auditory pathway (e.g. [17][18][19]), one of the most common forms of hearing loss is caused by the damage and/or loss of the sensory hair cells and the associated auditory neurons that make synaptic connections within the cochlea, which is collectively called sensorineural hearing loss (SNHL: [8,[20][21][22]). Currently, the only available options for ameliorating SNHL are hearing aids or cochlear implants.…”

Section: Introductionmentioning

confidence: 99%

Recent advances and future challenges in gene therapy for hearing loss

et al. 2023

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Hearing loss is the most common sensory deficit experienced by humans and represents one of the largest chronic health conditions worldwide. It is expected that around 10% of the world's population will be affected by disabling hearing impairment by 2050. Hereditary hearing loss accounts for most of the known forms of congenital deafness, and over 25% of adult-onset or progressive hearing loss. Despite the identification of well over 130 genes associated with deafness, there is currently no curative treatment for inherited deafness. Recently, several pre-clinical studies in mice that exhibit key features of human deafness have shown promising hearing recovery through gene therapy involving the replacement of the defective gene with a functional one. Although the potential application of this therapeutic approach to humans is closer than ever, substantial further challenges need to be overcome, including testing the safety and longevity of the treatment, identifying critical therapeutic time windows and improving the efficiency of the treatment. Herein, we provide an overview of the recent advances in gene therapy and highlight the current hurdles that the scientific community need to overcome to ensure a safe and secure implementation of this therapeutic approach in clinical trials.

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“…Sensorineural hearing loss (SNHL) can co-occur with tinnitus in both or the affected ear due to reduced sound transmission to hearing nerves in the brain. However, genomewide association studies (GWAS) and transcriptome-wide analysis studies (TWAS) in mice and humans do not correlate but have been reported that both hearing loss and tinnitus are polygenic disorders ( 3 ). In any case, tinnitus can be characterized by its intensity and frequency content that is gradual or instant onset, could be mild to severe, temporary or persistent, and permanent ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…The pathophysiology of tinnitus remains challenging, unclear, and poorly understood, and its diagnosis and treatment are complicated by its polygenic nature, with different associated mechanisms in the auditory pathways ( 3 ). This is because increased somatization and functional changes in auditory and non-auditory areas are involved in the pathophysiology of tinnitus ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

Endocannabinoid system components as potential neuroimmune therapeutic targets in tinnitus

2023

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Research interest in understanding tinnitus has increased severalfold in the last decade to find a cure for this auditory disorder. Hyperacusis can also accompany tinnitus, although the mechanisms involved in hyperacusis and tinnitus are different. Millions of people suffer from some degree of tinnitus with hearing loss. Tinnitus is believed to be a form of sensory epilepsy, spawning neuronal hyperactivity from the cochlear nucleus and inferior colliculus of the auditory brainstem region. Cannabis has been used for recreation, medicinal purposes, and served as an entheogen from time immemorial. With the current and increasing global medical and recreational cannabis legalization, there is renewed enthusiasm for the use of cannabinoid drugs, and the role of the endocannabinoid system (ECS) in several health disorders including tinnitus which is associated with COVID-19. The ECS signaling pathways have been proposed to affect the underlying pathophysiology of tinnitus. Cannabinoid receptors (CBRs) have been found in the auditory system, raising interest in ECS signaling in hearing and tinnitus. However, previous studies mostly in animal models of tinnitus did not investigate the involvement of CB2Rs but focused on CB1R-based responses, which suggested that CB1R ligands had no effect and may even be harmful and worsen tinnitus. With new molecular techniques and transgenic approaches used to dissect the complexity of the ECS, the role of ECS/CB2R neuroimmunological function in the auditory system and tinnitus is emerging. This perspective proposes the role of emerging neuroimmune crosstalk of the ECS in sound-sensing structures of the auditory system as a potential pharmacogenomic therapeutic target using cannabinoid CB2R ligands in tinnitus in the era of the COVID-19 pandemic.

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Hearing loss and tinnitus: association studies for complex-hearing disorders in mouse and man

Cited by 6 publications

References 92 publications

The Road Traveled and Journey Ahead for the Genetics and Genomics of Tinnitus

The Road Traveled and Journey Ahead for the Genetics and Genomics of Tinnitus

Recent advances and future challenges in gene therapy for hearing loss

Endocannabinoid system components as potential neuroimmune therapeutic targets in tinnitus

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