Journal of Regenerative Medicine ISSN: 2325-9620

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Research Article, J Regen Med Vol: 4 Issue: 1

Regeneration of Cochlear Hair Cells with Atoh1 Gene Therapy after Noise-Induced Hearing Loss

Andrew K Wise1-3, Brianna O Flynn1, Patrick J Atkinson4, James B Fallon1-3, Madeline Nicholson1 and Rachael T Richardson1-3*
1Bionics Institute, Melbourne, Australia
2Department of Otolaryngology, University of Melbourne, Melbourne, Australia
3Department of Medical Bionics University of Melbourne, Melbourne, Australia
4Department of Otolaryngology, School of Medicine, Stanford University, Stanford, CA, USA
Corresponding author : Dr. Rachael T Richardson
Bionics Institute, 384 Albert Street, East Melbourne, Victoria, 3002, Australia
Tel: +613 9667 7594; Fax: +613 9667 7518
E-mail: [email protected]
Received: January 07, 2015 Accepted: June 12, 2015 Published: June 18, 2015
Citation: Wise AK, Flynn BO, Atkinson PJ, Fallon JB, Nicholson M, et al. (2015) Regeneration of Cochlear Hair Cells with Atoh1 Gene Therapy after Noise- Induced Hearing Loss. J Regen Med 4:1. doi:10.4172/2325-9620.1000121

Abstract

Background: 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 myosin VIIa-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.

Keywords: Atoh1; Cochlea; Deafness; Gene therapy; Hair cells; Noise; Regeneration; Supporting cells

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