Genetic and pharmacological intervention for treatment/prevention of hearing loss
Genetic and pharmacological intervention for treatment/prevention of hearing loss
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DOI：
10.1016/j.jcomdis.2008.03.004
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发表时间：
2008-09-01
影响因子：
1.7
通讯作者：
Cotanche, Douglas A.
中科院分区：
文献类型：
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作者：
Cotanche, Douglas A.
20年前，首次证明鸟类在噪音损伤或氨基糖苷治疗后可以再生耳蜗毛细胞。了解这种结构和功能再生是如何发生的，可能会导致治疗人类感音神经性听力损失的疗法的发展。最近的实验表明，噪声暴露和氨基糖苷处理导致毛细胞凋亡。在鸟类中，这种程序性细胞死亡诱导邻近的支持细胞进行再生以取代丢失的毛细胞。虽然哺乳动物耳蜗毛细胞在噪声损伤和耳毒性药物治疗下发生凋亡，但其支持细胞不具备再生能力。然而，目前关于基因操作、基因治疗和干细胞移植的实验表明，哺乳动物耳蜗的再生最终是可能的，并且有一天可能为人类听力损失提供一种治疗工具。学习成果：读者应该能够：(1)描述鸟类和哺乳动物耳蜗的解剖结构，识别Corti器官中的单个细胞类型，并区分参与听力功能的主要特征；(2)展示声音损伤和氨基糖苷中毒如何诱导耳蜗毛细胞凋亡的知识；(3)定义鸟类耳蜗毛细胞丢失如何导致新的毛细胞再生，并将其与哺乳动物耳蜗区分出来，后者在损伤后没有再生。(4)解释新方法的潜力，如基因操作、基因治疗和干细胞移植，可以为哺乳动物耳蜗毛细胞丢失提供治疗方法，(C) 2008 Elsevier Inc.。版权所有。
Twenty years ago it was first demonstrated that birds could regenerate their cochlear hair cells following noise damage or aminoglycoside treatment. An understanding of how this structural and functional regeneration occurred might lead to the development of therapies for treatment of sensorineural hearing loss in humans. Recent experiments have demonstrated that noise exposure and aminoglycoside treatment lead to apoptosis of the hair cells. In birds, this programmed cell death induces the adjacent supporting cells to undergo regeneration to replace the lost hair cells. Although hair cells in the mammalian cochlea undergo apoptosis in response to noise damage and ototoxic drug treatment, the supporting cells do not possess the ability to undergo regeneration. However, current experiments on genetic manipulation, gene therapy, and stem cell transplantation suggest that regeneration in the mammalian cochlea may eventually be possible and may 1 day provide a therapeutic tool for hearing loss in humans.Learning outcomes: The reader should be able to: (1) Describe the anatomy of the avian and mammalian cochlea, identify the individual cell types in the organ of Corti, and distinguish major features that participate in hearing function, (2) Demonstrate a knowledge of how sound damage and aminoglycoside poisoning induce apoptosis of hair cells in the cochlea, (3) Define how hair cell loss in the avian cochlea leads to regeneration of new hair cells and distinguish this from the mammalian cochlea where there is no regeneration following damage, and (4) Interpret the potential for new approaches, such as genetic manipulation, gene therapy and stem cell transplantation, could provide a therapeutic approach to hair cell loss in the mammalian cochlea, (C) 2008 Elsevier Inc. All rights reserved.