BASIC RESEARCHES ON GENE TRANSFER FOR THE PROPHYLAXIS OF ACOUSTIC TRAUMA

预防声损伤的基因转移基础研究

基本信息

批准号：
11470359
负责人：
KANZAKI Jin
金额：
$ 4.22万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470359/
关键词：
ACOUSTIC TRAUMA GENE TRANSFER GDNF ADENO VIRUS SHAKER-2 MOUSE GUINEA PIG COCHLEA CDNF ヘルペスウイルスマウス

项目摘要

There are considerable evidences suggesting that cochlear hair cells are first damaged by acoustic trauma followed by secondary degeneration of the cochlear nerve. GDNF, a glial derived neurotrophic factor, has been known to exert a protective or prophylactic role against acoustic trauma. On the other hand, gene therapy is a powerful technology that may be applied for treating inner ear disease including acoustic trauma. Several studies have shown successful transduction of inner ear cells using viral vectors. In our first experiment, an infection of adenovirus vector was studied in the Shaker-2 mouse cochleae and vestibules. Adenovirus vector was found in the hair cells and supporting cells. There was no significant difference in the expression among the homo-, hetero- and wild types. The expression in the hair cells decreased from P1 to P5. In the second experiment, we investigated the distribution pattern of transferred GDNF in the cochlea using guinea pigs. As a result, GDNF was expressed in the spiral ganglion cells. GDNF was not expressed in the contra-lateral cochlea. In 5 weeks after the transfer of GDNF, more than 150〜200% of the spiral ganglion cells were survived compare to the control, which showed a statistically significant difference. Based upon these results we can conclude that the expression of GDNF induced by gene transfer has a role on protection or prophylaxis against the degeneration of spiral ganglion cells.

有大量证据表明，首先，耳蜗造成了耳蜗细胞，然后是人工耳蜗的继发性变性。 GDNF是一种神经胶质衍生的神经营养因子，已知可以针对声学创伤行使保护性或预防性作用。另一方面，基因疗法是一种强大的技术，可用于治疗包括声学创伤在内的内耳疾病。几项研究表明，使用病毒载体成功转导内耳细胞。在我们的第一个实验中，研究了腺病毒载体的感染在Shaker-2小鼠耳蜗和鉴赏物中。在毛细胞和支撑细胞中发现了腺病毒载体。同型，异源和野生类型之间的表达没有显着差异。毛细胞中的表达从P1到P5发展。在第二个实验中，我们研究了使用豚鼠在耳蜗中转移的GDNF的分布模式。结果，GDNF在螺旋神经节细胞中表达。 GDNF未在逆边耳蜗中表达。在GDNF转移后的5周内，与对照相比，超过150-200％的螺旋神经节细胞幸存下来，这表现出统计学上的显着差异。基于这些结果，我们可以包括基因转移诱导的GDNF的表达在针对螺旋神经节细胞变性的保护或预防中起作用。