Lalwani A K, Walsh B J, Carvalho G J, Muzyczka N, Mhatre A N
Department of Otolaryngology-Head & Neck Surgery, University of California San Francisco, 94143-0342, USA.
Am J Otol. 1998 May;19(3):390-5.
Adeno-associated virus (AAV) is a suitable viral vector for transgene expression within the mammalian vestibular organs.
In vivo introduction and expression of a foreign gene within the cochlear tissues have been established using a variety of viral vectors and guinea pig as the animal model. However, the vestibular neuroepithelia of the mammalian inner ear as a potential target for transgene expression remain to be investigated.
Transgene expression was assessed within the vestibular neuroepithelia of guinea pigs after intracochlear infusion of the recombinant AAV vector with the aid of an osmotic minipump. Evaluation of the transgene within the vestibular apparatus focused on its duration of expression from 2-24 weeks after intracochlear AAV infusion using immunohistochemistry.
In the AAV-beta-galactosidase (beta-gal)-infused animals, the sensory hair cells as well as the supporting epithelial cells of cristae and maculae were positive for the transgene expression. The relative level of beta-gal expression was noted to decrease progressively over time. Transduction of the vestibular neuroepithelia also was observed in the contralateral ear, a finding that has been documented previously in AAV-integrated transgene expression in the cochlea.
This study reports the first demonstration of introduction and long-term transgene expression within the vestibular neuroepithelia. The ability to express a foreign gene with the vestibular system allows the possibility of experimental and therapeutic application of gene therapy technology to address vestibular function and dysfunction.
腺相关病毒（AAV）是一种适用于在哺乳动物前庭器官内进行转基因表达的病毒载体。
利用多种病毒载体并以豚鼠作为动物模型，已实现了在耳蜗组织内对外源基因的体内导入和表达。然而，哺乳动物内耳的前庭神经上皮作为转基因表达的潜在靶点仍有待研究。
借助渗透微型泵将重组AAV载体经耳蜗内注入豚鼠后，评估前庭神经上皮内的转基因表达情况。利用免疫组织化学方法，重点评估耳蜗内注入AAV后2至24周内前庭器中转基因的表达持续时间。
在注入AAV-β-半乳糖苷酶（β-gal）的动物中，感觉毛细胞以及嵴和斑的支持上皮细胞的转基因表达呈阳性。β-gal表达的相对水平随时间逐渐下降。在对侧耳中也观察到了前庭神经上皮的转导，这一发现先前在耳蜗中AAV整合的转基因表达中已有记录。
本研究首次报道了在前庭神经上皮内导入并实现长期转基因表达。在前庭系统中表达外源基因的能力为基因治疗技术在解决前庭功能和功能障碍方面的实验和治疗应用提供了可能性。
