Mass transport in the inner-ear fluid

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PROJECT SUMMARY The inner-ear fluids, unlike other body fluids, are stationary and isolated from the rest of the body. These characteristics give opportunities and challenges in maintaining inner-ear health and in treating inner- ear diseases. Due to the blood-labyrinth barrier, systemic delivery of drugs to the inner ear is highly inefficient. On the other hand, this isolation is an opportunity—drugs can be delivered locally with minimal off-target concerns. Unfortunately, the potential advantage of local delivery has been difficult to capitalize on because of the labyrinthine geometry of the inner ear. Application of drug at any location of the inner ear labyrinth filled with stationary fluids results in high concentration at the application site without reaching distant locations. A current remedy is to create surgical holes in the temporal bone to allow inner-ear fluids to flow despite the risk of surgical damage. We propose minimally invasive and efficient drug delivery mechanism into the inner ear. Specifically, we will develop a method to use sounds as the agitating source for cochlear drug delivery. Recent data regarding OoC micromechanics are both exciting and controversial because new observations do not fit well into existing frameworks for cochlear biophysics. For example, the outer hair cells are widely-acknowledged as the actuator for cochlear amplification. However, the outer hair cells generate force most efficiently at frequencies below the characteristic frequency at most cochlear locations, raising the possibility of additional functions. The proposed project combines two topics that have previously been investigated independently—mechanics and fluid homeostasis of the OoC. By combining these two subjects, we propose the novel hypothesis that active outer hair cells enhance mass transport along the cochlea. We will test the hypothesis with three aims that combine physiological and computational modeling approaches. For Aim 1, experiments in live animals (gerbil) will be used to characterize the effect of sound and outer-hair-cell motility on mass (neurotoxin) transport along the length of the cochlear duct. Aim 2 experiments will use excised cochlear tissues implanted in a novel micro-fluidic chamber to characterize the OoC peristaltic vibrations due to outer-hair-cell motility. For Aim 3, new biophysical computer models will simulate drug delivery along the cochlea, thereby integrating physiological results from Aims 1 and 2. Approximately one out of five adults in the United States has some degree of hearing loss. Multiple common forms of hereditary, age-related, and noise-induced hearing loss are ascribed to malfunctions of cochlear-fluid homeostasis. By investigating cochlear-fluid homeostasis from an innovative point of view (mechanics), this project will provide an explanation on why hearing of high frequency sound is more vulnerable. In the long term, we have ambition to provide a remedy to delay/prevent hearing losses related to fluid-homeostasis.