Dataset Information

Hair cell regeneration after ATOH1 gene therapy in the cochlea of profoundly deaf adult guinea pigs.

ABSTRACT: The degeneration of hair cells in the mammalian cochlea results in permanent sensorineural hearing loss. This study aimed to promote the regeneration of sensory hair cells in the mature cochlea and their reconnection with auditory neurons through the introduction of ATOH1, a transcription factor known to be necessary for hair cell development, and the introduction of neurotrophic factors. Adenoviral vectors containing ATOH1 alone, or with neurotrophin-3 and brain derived neurotrophic factor were injected into the lower basal scala media of guinea pig cochleae four days post ototoxic deafening. Guinea pigs treated with ATOH1 gene therapy, alone, had a significantly greater number of cells expressing hair cell markers compared to the contralateral non-treated cochlea when examined 3 weeks post-treatment. This increase, however, did not result in a commensurate improvement in hearing thresholds, nor was there an increase in synaptic ribbons, as measured by CtBP2 puncta after ATOH1 treatment alone, or when combined with neurotrophins. However, hair cell formation and synaptogenesis after co-treatment with ATOH1 and neurotrophic factors remain inconclusive as viral transduction was reduced due to the halving of viral titres when the samples were combined. Collectively, these data suggest that, whilst ATOH1 alone can drive non-sensory cells towards an immature sensory hair cell phenotype in the mature cochlea, this does not result in functional improvements after aminoglycoside-induced deafness.

SUBMITTER: Atkinson PJ

PROVIDER: S-EPMC4103851 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Hair cell regeneration after ATOH1 gene therapy in the cochlea of profoundly deaf adult guinea pigs.

Atkinson Patrick J PJ Wise Andrew K AK Flynn Brianna O BO Nayagam Bryony A BA Richardson Rachael T RT

PloS one 20140718 7

The degeneration of hair cells in the mammalian cochlea results in permanent sensorineural hearing loss. This study aimed to promote the regeneration of sensory hair cells in the mature cochlea and their reconnection with auditory neurons through the introduction of ATOH1, a transcription factor known to be necessary for hair cell development, and the introduction of neurotrophic factors. Adenoviral vectors containing ATOH1 alone, or with neurotrophin-3 and brain derived neurotrophic factor were ...[more]

PMID: 25036727

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Project description:BackgroundPrevious research has been designed to study the effect of hearing loss on supra-second duration estimation in the visual channel and position effect of visual abilities among deaf populations. The current study aimed to investigate the sub-second duration perception of different visual fields in profoundly deaf individuals.MethodsA total of 16 profoundly deaf undergraduates and 16 hearing undergraduates completed a visual duration bisection task in which participants made judgments about whether a series of probe durations that were linearly spaced from 200 ms to 800 ms at 100 ms intervals were more similar to a standard short duration (200 ms) or a standard long duration (800 ms). The probe stimuli were presented in the center, left, or right of the screen. A repeated measure analysis of variance (ANOVA) with a between-participants factor of group and a within-participants factor of position, and a one-sample t-test were conducted.ResultsThe Weber ratio (WR) values of deaf participants were significantly higher than those of hearing participants, regardless of the presented positions of the visual stimulus. The bisection point (BP) value of deaf participants was significantly lower than 500 ms (average mean of 200/800 ms) and the BP value of hearing participants did not significantly differ from 500 ms, although the overall difference of BP values between the deaf group and hearing group did not reach significance. For deaf participants, the BP value in the center condition was significantly lower than 500 ms; however, the difference between the BP value in the left condition and 500 ms did not reach significance, indicating that their duration discrimination accuracy in the left visual field was better than that in the center visual field.ConclusionsHearing loss impaired visual sub-second duration perception, and deaf individuals showed a left visual field advantage of duration discrimination accuracy during the visual duration bisection task.

Dataset Information

Hair cell regeneration after ATOH1 gene therapy in the cochlea of profoundly deaf adult guinea pigs.

Publications

Hair cell regeneration after ATOH1 gene therapy in the cochlea of profoundly deaf adult guinea pigs.

Similar Datasets

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