Talaei Sara, Schnee Michael E, Aaron Ksenia A, Ricci Anthony J
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United States.
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, United States.
Front Cell Neurosci. 2019 Oct 30;13:471. doi: 10.3389/fncel.2019.00471. eCollection 2019.
The inner ear houses the sensory epithelium responsible for vestibular and auditory function. The sensory epithelia are driven by pressure and vibration of the fluid filled structures in which they are embedded so that understanding the homeostatic mechanisms regulating fluid dynamics within these structures is critical to understanding function at the systems level. Additionally, there is a growing need for drug delivery to the inner ear for preventive and restorative treatments to the pathologies associated with hearing and balance dysfunction. We compare drug delivery to neonatal and adult inner ear by injection into the posterior semicircular canal (PSCC) or through the round window membrane (RWM). PSCC injections produced higher levels of dye delivery within the cochlea than did RWM injections. Neonatal PSCC injections produced a gradient in dye distribution; however, adult distributions were relatively uniform. RWM injections resulted in an early base to apex gradient that became more uniform over time, post injection. RWM injections lead to higher levels of dye distributions in the brain, likely demonstrating that injections can traverse the cochlea aqueduct. We hypothesize the relative position of the cochlear aqueduct between injection site and cochlea is instrumental in dictating dye distribution within the cochlea. Dye distribution is further compounded by the ability of some chemicals to cross inner ear membranes accessing the blood supply as demonstrated by the rapid distribution of gentamicin-conjugated Texas red (GTTR) throughout the body. These data allow for a direct evaluation of injection mode and age to compare strengths and weaknesses of the two approaches.
内耳包含负责前庭和听觉功能的感觉上皮。感觉上皮由其所处的充满液体的结构的压力和振动驱动,因此了解调节这些结构内流体动力学的稳态机制对于从系统层面理解功能至关重要。此外,越来越需要将药物输送到内耳,以对与听力和平衡功能障碍相关的病症进行预防性和恢复性治疗。我们通过注射到后半规管(PSCC)或通过圆窗膜(RWM)将药物输送到新生和成年内耳进行比较。与RWM注射相比,PSCC注射在耳蜗内产生的染料输送水平更高。新生动物的PSCC注射产生了染料分布梯度;然而,成年动物的分布相对均匀。RWM注射导致早期从基部到顶部的梯度,注射后随着时间推移变得更加均匀。RWM注射导致染料在脑内的分布水平更高,这可能表明注射可以穿过蜗水管。我们假设蜗水管在注射部位和耳蜗之间的相对位置有助于决定染料在耳蜗内的分布。正如庆大霉素偶联德克萨斯红(GTTR)在全身的快速分布所示,一些化学物质穿过内耳膜进入血液供应的能力进一步使染料分布复杂化。这些数据允许直接评估注射方式和年龄,以比较两种方法的优缺点。