Lue Po-Yi, Oliver Mark H, Neeff Michel, Thorne Peter R, Suzuki-Kerr Haruna
Department of Physiology, The University of Auckland, Auckland, New Zealand.
Eisdell Moore Centre, The University of Auckland, Auckland, New Zealand.
Lab Anim Res. 2023 Nov 27;39(1):31. doi: 10.1186/s42826-023-00182-3.
Sensorineural hearing loss (SNHL), caused by pathology in the cochlea, is the most common type of hearing loss in humans. It is generally irreversible with very few effective pharmacological treatments available to prevent the degenerative changes or minimise the impact. Part of this has been attributed to difficulty of translating "proof-of-concept" for novel treatments established in small animal models to human therapies. There is an increasing interest in the use of sheep as a large animal model. In this article, we review the small and large animal models used in pre-clinical hearing research such as mice, rats, chinchilla, guinea pig, rabbit, cat, monkey, dog, pig, and sheep to humans, and compare the physiology, inner ear anatomy, and some of their use as model systems for SNHL, including cochlear implantation surgeries. Sheep have similar cochlear anatomy, auditory threshold, neonatal auditory system development, adult and infant body size, and number of birth as humans. Based on these comparisons, we suggest that sheep are well-suited as a potential translational animal model that bridges the gap between rodent model research to the clinical use in humans. This is especially in areas looking at changes across the life-course or in specific areas of experimental investigation such as cochlear implantation and other surgical procedures, biomedical device development and age-related sensorineural hearing loss research. Combined use of small animals for research that require higher throughput and genetic modification and large animals for medical translation could greatly accelerate the overall translation of basic research in the field of auditory neuroscience from bench to clinic.
感音神经性听力损失（SNHL）由耳蜗病变引起，是人类最常见的听力损失类型。它通常是不可逆的，几乎没有有效的药物治疗方法来预防退行性变化或最小化其影响。部分原因在于难以将在小动物模型中确立的新治疗方法的“概念验证”转化为人类疗法。人们对将绵羊用作大型动物模型的兴趣与日俱增。在本文中，我们综述了临床前听力研究中使用的小动物和大动物模型，如小鼠、大鼠、毛丝鼠、豚鼠、兔子、猫、猴子、狗、猪和绵羊，并将它们与人类进行比较，还比较了它们的生理学、内耳解剖结构以及作为SNHL模型系统的一些用途，包括人工耳蜗植入手术。绵羊的耳蜗解剖结构、听觉阈值、新生儿听觉系统发育、成年和婴儿体型以及产仔数量与人类相似。基于这些比较，我们认为绵羊非常适合作为一种潜在的转化动物模型，弥合啮齿动物模型研究与人类临床应用之间的差距。这尤其适用于研究生命历程中的变化或特定实验研究领域，如人工耳蜗植入和其他外科手术、生物医学设备开发以及与年龄相关的感音神经性听力损失研究。将需要更高通量和基因改造的研究用小动物与用于医学转化的大动物结合使用，可以极大地加速听觉神经科学领域基础研究从实验室到临床的整体转化。
