Molecular biological investigation for the regeneration of inner ear sensory cells by controlling freeradical and apoptosis

本研究的目的是探讨自由基(NO、ROS)和细胞凋亡在内耳疾病中的作用，并通过调节和/或抑制内耳疾病机制的各个步骤来开发治疗内耳疾病的新方法。随后，感觉细胞开始通过细胞凋亡而死亡。钙蛋白酶和半胱氨酸天冬氨酸氨基转移酶可能在细胞凋亡中起重要作用。这些机制被认为是几乎所有内耳疾病的共同途径。基于这些结果，我们研究了通过清除自由基、抑制半胱氨酸天冬氨酸酶或钙蛋白酶和添加神经营养因子来减轻内耳疾病的作用。所有药物对毛细胞的损伤都是有限的，联合应用如抑制自由基、神经营养素、抑制自由基、钙蛋白酶或半胱氨酸天冬氨酸酶抑制剂，对毛细胞损伤的预防作用更强。在这些基础研究的基础上，我们应用自由基清除剂(瑞巴匹特、维生素C、谷胱甘肽)治疗控制不佳的梅尼埃病、顺铂耳毒性和老年性耳聋。这些临床试验的结果充分显示了听力的改善。这些结果被提交给会议(第13和14届日本耳科学会会议，第62和63届日本平衡研究学会会议，第40届内耳生物学研讨会)，并由10篇论文提交

The aim of this study is to investigate the effects of free radicals (NO,ROS) and apoptosis to the inner ear disorders and to develop the new treatments for the inner ear disease by modulating and/or inhibiting the various steps of the mechanisms of inner ear disorders.As a result, certain stimuli induce the formation of free radicals, such as NO,ROS, resulting in a damage of inner ear. Subsequently, the sensory cells began to death by apoptosis. Calpain and caspase may play an important role for the apoptosis. These mechanisms were suggested to be a common pathway for almost all inner ear disorders. Based on these results, we investigated the attenuation of inner ear disorders by scavenging free radicals, inhibition of caspase or calpain and the addition of neurotrophines. All drugs used limited the hair cell damage and the combinations of drugs, such as inhibition of free radicals + neurotrophine, inhibition of free radicals + calpain or caspase inhibitors, had a significantly stronger preventive effect on hair cell damage. Based on these basic research, we have applied radical scavengers (rebamipide, vitamin C, glutathione) to the poor controlled Meniere's disease, cisplatin ototoxicity and presbyacusis. The results of these clinical trials are sufficient revealing an improvement of hearing.These results were presented at the meetings (13th and 14th meeting of the Otological Society of Japan, 62th and 63th meeting of Japan Society for Equilibrium Reseach, 40th Workshop on Inner Ear Biology) and were presented by 10 papers