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Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity

Gene Therapy volume 7, pages 1046–1054 (2000)Cite this article

Abstract

Gentamicin administration often results in cochlear and/or vestibular hair cell loss and hearing and balance impairment. It has been demonstrated that adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor (GDNF) can protect cochlear hair cells against ototoxic injury. In this study, we evaluated the protective effects of adenovirus-mediated overexpression of GDNF against gentamicin ototoxicity. An adenovirus vector expressing the human GDNF gene (Ad.GDNF) was administered into the scala vestibuli as a rescue agent at the same time as gentamicin, or as a protective agent, 7 days before gentamicin administration. Animals in the Rescue group displayed hearing thresholds that were significantly better than those measured in the Gentamicin or Ad.LacZ/Gentamicin groups. In the Protection group, Ad.GDNF afforded significant preservation of utricular hair cells. The data demonstrated protection of the inner ear structure, and rescue of the inner ear structure and function against ototoxic insults. These experiments suggest that inner ear gene therapy may be developed as a clinical tool for protecting the ear against environmentally induced insults.

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Acknowledgements

We wish to thank Timo Stöver for helpful discussions and Joseph E Hawkins for valuable comments on the manuscript. AL Miller is funded by a Rackham Predoctoral Fellowship. This study was supported by NIH-NIDCD grants PO1 DC00078 and R01 DC01634 (YR).

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Authors and Affiliations

  1. Kresge Hearing Research Institute, The University of Michigan, Ann Arbor, MI, USA

    M Suzuki, M Yagi, JN Brown, AL Miller, JM Miller & Y Raphael

  2. Department of Otolaryngology, University of Tokyo, Tokyo, Japan

    M Suzuki

  3. Department of Otolaryngology, Kansai Medical University, Osaka, Japan

    M Yagi

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  1. M Suzuki
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  2. M Yagi
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Suzuki, M., Yagi, M., Brown, J. et al. Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity. Gene Ther 7, 1046–1054 (2000). https://doi.org/10.1038/sj.gt.3301180

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