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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.

大量证据表明，耳蜗毛细胞首先受到声损伤，随后耳蜗神经发生继发性变性。GDNF是一种胶质源性神经营养因子，对声损伤具有保护或预防作用。另一方面，基因治疗是一种强大的技术，可用于治疗包括声损伤在内的内耳疾病。几项研究已经显示使用病毒载体成功转导内耳细胞。在我们的第一个实验中，研究了腺病毒载体在Shaker-2小鼠耳蜗和前庭中的感染。在毛细胞和支持细胞中发现腺病毒载体。同源、异型和野生型之间的表达无显著差异。从P1到P5，毛细胞中的表达减少。在第二个实验中，我们研究了转移的GDNF在豚鼠耳蜗中的分布模式。结果表明，GDNF在螺旋神经节细胞中表达。GDNF在对侧耳蜗不表达。GDNF转染后5周，螺旋神经节细胞存活率为150 ~ 200%，与对照组比较差异有统计学意义。根据这些结果，我们可以得出结论，GDNF基因转移诱导的表达对螺旋神经节细胞的变性具有保护或预防作用。