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奥克兰在嘌呤能信号传导与内耳治疗方面的听力科学发现与转化。

Auckland hearing science discovery and translation in purinergic signaling and inner ear therapeutics.

作者信息

Vlajkovic Srdjan M, Housley Gary D, Thorne Peter R

机构信息

Department of Physiology, Section of Audiology and The Eisdell Moore Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.

Translational Neuroscience Facility and Department of Physiology, School of Biomedical Sciences, UNSW Sydney, Sydney, NSW, Australia.

出版信息

J R Soc N Z. 2024 Jun 3;55(3):405-423. doi: 10.1080/03036758.2024.2359945. eCollection 2025.

Abstract

The inner ear is a complex sensory organ responsible for hearing and balance. It is deeply embedded in the temporal bone with challenging access for diagnostic and therapeutic purposes. Stress and injury to the peripheral hearing organ (cochlea) lead to temporary or permanent sensorineural hearing loss (SNHL), which is the most common form of hearing loss resulting from cellular and molecular damage to the sensory hair cells and primary auditory neurons in the spiral ganglion. These cells cannot regenerate, and their loss leads to hearing disability. Hearing aids can amplify sound and improve residual hearing ability but cannot restore function; therefore, alternative therapies are urgently needed. The pharmacological approach to treating SNHL has been our mainstream research over the past two decades. This review describes our studies investigating the purinergic signalling system in the cochlea and its implications for inner ear therapies. Using animal models of SNHL, we have established that purinergic P1 (adenosine) and P2 (ATP) receptors can prevent or mitigate cochlear injury by reducing cochlear sensitivity to loud sound and improving the survival of sensorineural tissues. Here, we highlight our research investigating the therapeutic potential of P1 and P2 receptor agonists and antagonists in inner ear disorders.

摘要

内耳是一个负责听觉和平衡的复杂感觉器官。它深深嵌入颞骨中,诊断和治疗时难以触及。外周听觉器官(耳蜗)受到的压力和损伤会导致暂时性或永久性感音神经性听力损失(SNHL),这是感觉毛细胞和螺旋神经节中的初级听觉神经元发生细胞和分子损伤导致的最常见听力损失形式。这些细胞无法再生,它们的丧失会导致听力残疾。助听器可以放大声音并提高残余听力,但无法恢复功能;因此,迫切需要替代疗法。在过去二十年中,药物治疗SNHL一直是我们的主流研究方向。这篇综述描述了我们对耳蜗中嘌呤能信号系统及其在内耳治疗中的意义的研究。通过使用SNHL动物模型,我们已经证实嘌呤能P1(腺苷)和P2(ATP)受体可以通过降低耳蜗对大声的敏感性和提高感觉神经组织的存活率来预防或减轻耳蜗损伤。在此,我们重点介绍我们对P1和P2受体激动剂和拮抗剂在内耳疾病中的治疗潜力的研究。

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