Regeneration of cochlear hair cells with Atoh1 gene therapy after noise-induced hearing loss

Simple item page
dc.contributor.authorWise, Andrew
dc.contributor.authorFlynn, Brianna
dc.contributor.authorAtkinson, Patrick
dc.contributor.authorFallon, James
dc.contributor.authorNicholson, Madeline
dc.contributor.authorRichardson, Rachael
dc.date.accessioned2015-12-20T22:32:40Z
dc.date.available2015-12-20T22:32:40Z
dc.date.issued2015-06
dc.description.abstractBackground: Degeneration of hair cells in the mammalian cochlea results in irreversible hearing loss with no current treatment options to regain lost hair cell function. The Atoh1 gene is necessary for hair cell development and recent research has shown that Atoh1 gene therapy promotes new hair cell formation and hearing restoration in adult rodent deafness models. Objective: The aim of this study was to examine new hair cell formation via Atoh1 gene therapy in noise-deafened adult guinea pigs. Methods: Guinea pigs were deafened by noise exposure (130 dB, 11-13 kHz, 2 hours). After two weeks, the left cochleae were injected with an adenoviral vector containing the Atoh1 gene. Control animals were injected with a control adenoviral vector. Three weeks after injection cochleae were assessed for hair cell density, maturity and hair cell synaptogenesis with auditory neurons. Hearing thresholds were assessed throughout. Results: There were significantly more myosinVIIa-positive hair cells in cochleae that received Atoh1 gene therapy compared to contralateral cochleae and compared to cochleae that received control gene therapy (p<0.05 one way ANOVA). However, the number of hair cells in Atoh1-treated animals was far below normal. Expression of Atoh1 had a significant preservation effect on the cytoarchitecture of the sensory epithelium compared to controls (p<0.001 one way ANOVA). Expression of the synaptic protein CtBP2 was present in some transfected cells from Atoh1-injected guinea pigs but at a reduced density compared to normal cochleae. There was evidence of auditory neuron preservation near transfected hair cells in Atoh1-injected cochleae (p<0.05 one way ANOVA), but there were no improvements in hearing thresholds. Conclusion: This study supports growing evidence that new hair cell formation is possible in mature cochleae that have been severely damaged, in this case by noise, and demonstrates a protective influence of Atoh1 gene therapy on the immediate surrounding cellular environment.en_US
dc.identifier.citationAK Wise, BO Flynn, PJ Atkinson, JB Fallon, M Nicholson and RT Richardson (2015). Regeneration of cochlear hair cells with Atoh1 gene therapy after noise-induced hearing loss. Journal of Regenerative Medicine 4:1en_US
dc.identifier.urihttp://repository.bionicsinstitute.org:8080/handle/123456789/146
dc.publisherSciTechnolen_US
dc.subjectAtoh1en_US
dc.subjectcochleaen_US
dc.subjectdeafnessen_US
dc.subjectgene therapyen_US
dc.subjecthair cellsen_US
dc.subjectnoiseen_US
dc.subjectregenerationen_US
dc.subjectsupporting cellsen_US
dc.titleRegeneration of cochlear hair cells with Atoh1 gene therapy after noise-induced hearing lossen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
2015-06 Wise - Regeneration.pdf
Size:
1.13 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
BI publications