BASIC RESEARCHES ON GENE TRANSFER FOR THE PROPHYLAXIS OF ACOUSTIC TRAUMA

点击翻译按钮获取中文摘要

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.