期刊
MOLECULAR THERAPY
卷 18, 期 6, 页码 1111-1122出版社
CELL PRESS
DOI: 10.1038/mt.2010.28
关键词
-
资金
- Royal National Institute for Deaf People
- Garnett Passe and Rodney Williams Memorial Foundation
- NIDCD [HHS-N-263-2007-00053-c, DC-006437, P30 DC-04661]
- NICHHD [P30 HD-02774]
- Hearing Regeneration Initiative and Veterans' Hospital Administration
- Victorian Government
- RNID [G39] Funding Source: researchfish
- NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS [K08DC006437, P30DC004661] Funding Source: NIH RePORTER
A cochlear implant may be used to electrically stimulate spiral ganglion neurons (SGNs) in people with severe sensorineural hearing loss (SNHL). However, these neurons progressively degenerate after SNHL due to loss of neurotrophins normally supplied by sensory hair cells (HCs). Experimentally, exogenous neurotrophin administration prevents SGN degeneration but can also result in abnormal resprouting of their peripheral fibers. This study aimed to create a target-derived neurotrophin source to increase neuron survival and redirect fiber resprouting following SNHL. Adenoviral (Ad) vectors expressing green fluorescent protein (GFP) alone or in combination with brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT3) were injected into the cochlear scala tympani or scala media of guinea-pigs (GPs) deafened via aminoglycosides for 1 week. After 3 weeks, cochleae were examined for gene expression, neuron survival, and the projection of peripheral fibers in response to gene expression. Injection of vectors into the scala media resulted in more localized gene expression than scala tympani injection with gene expression consistently observed within the partially degenerated organ of Corti. There was also greater neuron survival and evidence of localized fiber responses to neurotrophin-expressing cells within the organ of Corti from scala media injections (P < 0.05), a first step in promoting organized resprouting of auditory peripheral fibers via gene therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据