DSpace

About the Bionics Institute

 

Bionics Institute Research Online >
Bionic Hearing >
Bionic Hearing Research Publications >


Title: Hair Cell Regeneration after ATOH1 Gene Therapy in the Cochlea of Profoundly Deaf Adult Guinea Pigs
Authors: Atkinson, Patrick
Wise, Andrew
Flynn, Brianna
Nayagam, Bryony
Richardson, Rachael
Keywords: Hair Cell Regeneration
Gene Therapy
ATOH1
Profound Deafness
Issue Date: 18-Jul-2014
Publisher: PLoS ONE
Citation: 2. Atkinson, P. J., Wise, A. K., Flynn, B. O., Nayagam, B. A. & Richardson, R. T. (2014). Hair cell regeneration after ATOH1 gene therapy in the cochlea of profoundly deaf adult guinea pigs. PLoS ONE 9, e102077.
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.
URI: http://repository.bionicsinstitute.org:8080/handle/123456789/90
Appears in Collections:Bionic Hearing Research Publications

Files in This Item:

File Description SizeFormat
2014-Atkinson-HairCellRegenATOH1.pdf10.83 MBAdobe PDFView/Open
View Statistics

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

DSpace Software Copyright © 2002-2010  Duraspace -