Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea.
The hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. These delicate stereocilia are susceptible to acoustic trauma and ototoxic drugs. While hair cells in lower vertebrates and the mammalian vestibular system can spontaneously...
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| Format: | Article |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3459923?pdf=render |
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| author | Shi-Ming Yang Wei Chen Wei-Wei Guo Shuping Jia Jian-He Sun Hui-Zhan Liu Wie-Yen Young David Z Z He |
| author_facet | Shi-Ming Yang Wei Chen Wei-Wei Guo Shuping Jia Jian-He Sun Hui-Zhan Liu Wie-Yen Young David Z Z He |
| author_sort | Shi-Ming Yang |
| collection | DOAJ |
| description | The hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. These delicate stereocilia are susceptible to acoustic trauma and ototoxic drugs. While hair cells in lower vertebrates and the mammalian vestibular system can spontaneously regenerate lost stereocilia, mammalian cochlear hair cells no longer retain this capability. We explored the possibility of regenerating stereocilia in the noise-deafened guinea pig cochlea by cochlear inoculation of a viral vector carrying Atoh1, a gene critical for hair cell differentiation. Exposure to simulated gunfire resulted in a 60-70 dB hearing loss and extensive damage and loss of stereocilia bundles of both inner and outer hair cells along the entire cochlear length. However, most injured hair cells remained in the organ of Corti for up to 10 days after the trauma. A viral vector carrying an EGFP-labeled Atoh1 gene was inoculated into the cochlea through the round window on the seventh day after noise exposure. Auditory brainstem response measured one month after inoculation showed that hearing thresholds were substantially improved. Scanning electron microscopy revealed that the damaged/lost stereocilia bundles were repaired or regenerated after Atoh1 treatment, suggesting that Atoh1 was able to induce repair/regeneration of the damaged or lost stereocilia. Therefore, our studies revealed a new role of Atoh1 as a gene critical for promoting repair/regeneration of stereocilia and maintaining injured hair cells in the adult mammal cochlea. Atoh1-based gene therapy, therefore, has the potential to treat noise-induced hearing loss if the treatment is carried out before hair cells die. |
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| id | doaj.art-312c6d9cc69448279a6020df4794d68c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T11:33:31Z |
| publishDate | 2012-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-312c6d9cc69448279a6020df4794d68c2022-12-21T23:47:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4635510.1371/journal.pone.0046355Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea.Shi-Ming YangWei ChenWei-Wei GuoShuping JiaJian-He SunHui-Zhan LiuWie-Yen YoungDavid Z Z HeThe hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. These delicate stereocilia are susceptible to acoustic trauma and ototoxic drugs. While hair cells in lower vertebrates and the mammalian vestibular system can spontaneously regenerate lost stereocilia, mammalian cochlear hair cells no longer retain this capability. We explored the possibility of regenerating stereocilia in the noise-deafened guinea pig cochlea by cochlear inoculation of a viral vector carrying Atoh1, a gene critical for hair cell differentiation. Exposure to simulated gunfire resulted in a 60-70 dB hearing loss and extensive damage and loss of stereocilia bundles of both inner and outer hair cells along the entire cochlear length. However, most injured hair cells remained in the organ of Corti for up to 10 days after the trauma. A viral vector carrying an EGFP-labeled Atoh1 gene was inoculated into the cochlea through the round window on the seventh day after noise exposure. Auditory brainstem response measured one month after inoculation showed that hearing thresholds were substantially improved. Scanning electron microscopy revealed that the damaged/lost stereocilia bundles were repaired or regenerated after Atoh1 treatment, suggesting that Atoh1 was able to induce repair/regeneration of the damaged or lost stereocilia. Therefore, our studies revealed a new role of Atoh1 as a gene critical for promoting repair/regeneration of stereocilia and maintaining injured hair cells in the adult mammal cochlea. Atoh1-based gene therapy, therefore, has the potential to treat noise-induced hearing loss if the treatment is carried out before hair cells die.http://europepmc.org/articles/PMC3459923?pdf=render |
| spellingShingle | Shi-Ming Yang Wei Chen Wei-Wei Guo Shuping Jia Jian-He Sun Hui-Zhan Liu Wie-Yen Young David Z Z He Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea. PLoS ONE |
| title | Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea. |
| title_full | Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea. |
| title_fullStr | Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea. |
| title_full_unstemmed | Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea. |
| title_short | Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea. |
| title_sort | regeneration of stereocilia of hair cells by forced atoh1 expression in the adult mammalian cochlea |
| url | http://europepmc.org/articles/PMC3459923?pdf=render |
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