A DPOAE assessment of outer hair cell integrity in ears with age-related hearing loss

Ueberfuhr, Margarete A.; Fehlberg, Hannah; Goodman, Shawn S.; Withnell, Robert H.

doi:10.1016/j.heares.2015.11.006

Cited by 20 publications

(7 citation statements)

References 46 publications

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“…As expected, in the elderly the amplitudes are lower for both types of evoked responses (TE and DP), which is a sign of hypofunction of the outer hair cell populations common in aging (Helleman et al, 2010). Lower amplitudes are accompanied by a lower number of functional outer hair cell populations (Mazelová et al, 2003; Ueberfuhr et al, 2016). The outer hair cell hypofunction in the elderly causes a deterioration of the auditory input that leads to a diminished neural signal reaching the central auditory structures.…”

Section: Discussionmentioning

confidence: 99%

Functional Age-Related Changes Within the Human Auditory System Studied by Audiometric Examination

Profant

Jilek

Bureš

et al. 2019

Front. Aging Neurosci.

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Age related hearing loss (presbycusis) is one of the most common sensory deficits in the aging population. The main subjective ailment in the elderly is the deterioration of speech understanding, especially in a noisy environment, which cannot solely be explained by increased hearing thresholds. The examination methods used in presbycusis are primarily focused on the peripheral pathologies (e.g., hearing sensitivity measured by hearing thresholds), with only a limited capacity to detect the central lesion. In our study, auditory tests focused on central auditory abilities were used in addition to classical examination tests, with the aim to compare auditory abilities between an elderly group (elderly, mean age 70.4 years) and young controls (young, mean age 24.4 years) with clinically normal auditory thresholds, and to clarify the interactions between peripheral and central auditory impairments. Despite the fact that the elderly were selected to show natural age-related deterioration of hearing (auditory thresholds did not exceed 20 dB HL for main speech frequencies) and with clinically normal speech reception thresholds (SRTs), the detailed examination of their auditory functions revealed deteriorated processing of temporal parameters [gap detection threshold (GDT), interaural time difference (ITD) detection] which was partially responsible for the altered perception of distorted speech (speech in babble noise, gated speech). An analysis of interactions between peripheral and central auditory abilities, showed a stronger influence of peripheral function than temporal processing ability on speech perception in silence in the elderly with normal cognitive function. However, in a more natural environment mimicked by the addition of background noise, the role of temporal processing increased rapidly.

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Section: Discussionmentioning

confidence: 99%

Functional Age-Related Changes Within the Human Auditory System Studied by Audiometric Examination

Profant

Jilek

Bureš

et al. 2019

Front. Aging Neurosci.

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“…The pathomechanism of ARHL involves metabolic and sensory damage along with neurodegeneration in the outer hair cells (OHCs), ribbon synapses, basement membrane, and stria vascularis 11 - 14 . One of the mechanistic causes of ARHL is OHC degeneration, which can occur with aging and results in the loss of otoacoustic emission responses 15 , 16 . In humans, the occurrence and extent of age-related OHC loss and ARHL are affected by genetic variants of KCNQ4, which encodes a voltage-gated potassium channel (Kv7.4) that is highly expressed in the basolateral membrane of OHCs and mediates the M-potassium current 17 , 18 .…”

Section: Introductionmentioning

confidence: 99%

In vivo outer hair cell gene editing ameliorates progressive hearing loss in dominant-negative Kcnq4 murine model

Noh

Rim²,

Gopalappa

et al. 2022

Theranostics

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Outer hair cell (OHC) degeneration is a major cause of progressive hearing loss and presbycusis. Despite the high prevalence of these disorders, targeted therapy is currently not available. Methods: We generated a mouse model harboring Kcnq4 W276S/+ to recapitulate DFNA2, a common genetic form of progressive hearing loss accompanied by OHC degeneration. After comprehensive optimization of guide RNAs, Cas9s, vehicles, and delivery routes, we applied in vivo gene editing strategy to disrupt the dominant-negative allele in Kcnq4 and prevent progressive hearing loss. Results: In vivo gene editing using a dual adeno-associated virus package targeting OHCs significantly improved auditory thresholds in auditory brainstem response and distortion-product otoacoustic emission. In addition, we developed a new live-cell imaging technique using thallium ions to investigate the membrane potential of OHCs and successfully demonstrated that mutant allele disruption resulted in more hyperpolarized OHCs, indicating elevated KCNQ4 channel activity. Conclusion: These findings can facilitate the development of targeted therapies for DFNA2 and support the use of CRISPR-based gene therapy to rectify defects in OHCs.

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“…D. M. Mills (2006) showed increased DPOAE thresholds and lower emission amplitudes in gerbil models of age-related hearing loss compared with controls, with weaker DPOAEs at higher frequencies for sensory hearing loss and weaker DPOAEs across frequencies for metabolic hearing loss. These distinctions may be difficult to obtain in small, heterogeneous human OAE data sets with a mixture of metabolic and sensory losses ( Ueberfuhr, Fehlberg, Goodman, & Withnell, 2016 ). In a larger sample with 432 older adults, Gates, Mills, Nam, Agostino, and Rubel (2002) reported a relatively stronger association between age and hearing sensitivity versus age and growth function metrics (DPOAE input/output), which suggested that outer hair cell damage did not account for age-related hearing loss.…”

Section: Introductionmentioning

confidence: 99%

Transient-Evoked Otoacoustic Emissions Reflect Audiometric Patterns of Age-Related Hearing Loss

2018

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Distinct forms of age-related hearing loss are hypothesized based on evidence from animal models of aging, which are identifiable in human audiograms. The Sensory phenotype results from damage (e.g., excessive noise or ototoxic drugs) to outer hair cells and sometimes inner hair cells, producing large threshold increases predominately at high frequencies. The Metabolic phenotype results from a decline in endocochlear potential that can reduce outer hair cell motility throughout the cochlea, producing gradually sloping thresholds from lower to higher frequencies. Finally, the combined Metabolic + Sensory phenotype results in low-frequency losses similar to the Metabolic phenotype and high-frequency losses similar to the Sensory phenotype. Because outer hair cell function appears to be affected differently in each phenotype, this study used audiograms from 618 adults aged 50 to 93 years (n = 1,208 ears) to classify phenotypes and characterize differences in transient-evoked otoacoustic emission (TEOAE) data. Significant phenotype differences were observed in frequency-band TEOAEs and configuration (intercept and slope), including large and broadly distributed TEOAE reductions for Metabolic and Metabolic + Sensory ears and more focused high-frequency TEOAE reductions for Sensory ears. These findings are consistent with metabolic declines that reduce cochlear amplification across a broad range of frequencies and more basally situated, high-frequency declines in sensory hearing loss. The results provide further validation for the classification of age-related hearing loss phenotypes based on audiograms and show human TEOAE declines that are highly consistent with animal models.

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A DPOAE assessment of outer hair cell integrity in ears with age-related hearing loss

Cited by 20 publications

References 46 publications

Functional Age-Related Changes Within the Human Auditory System Studied by Audiometric Examination

Functional Age-Related Changes Within the Human Auditory System Studied by Audiometric Examination

In vivo outer hair cell gene editing ameliorates progressive hearing loss in dominant-negative Kcnq4 murine model

Transient-Evoked Otoacoustic Emissions Reflect Audiometric Patterns of Age-Related Hearing Loss

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