Abstract
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.
Highlights
Inner ear end organs contain the sensory epithelium for balance and hearing
The fluid filled inner ear consists of discreetly positioned sensory epithelium of the vestibular and auditory systems housed in a contiguous membranous compartment (Sterkers et al, 1982; Hudspeth, 1989)
The bony capsule is filled with perilymph, a solution very similar to cerebral spinal fluid, and surrounds a membranous labyrinth containing endolymph, a high potassium, and low calcium solution created by supporting cells within each end organ (Sterkers et al, 1988; Wangemann and Schacht, 1996)
Summary
Inner ear end organs contain the sensory epithelium for balance and hearing. These fluid filled compartments are exquisitely sensitive to motion, the fluid motion within these end organs (Hudspeth, 1989). Understanding fluid flow and compartmentalization within these systems is important at multiple levels. Many pathologies associated with hearing loss and balance disorders stem from disruption of these fluid compartments or the pressure associated with these compartments [e.g., Meniere’s disease (Hornibrook and Bird, 2016), Superior Semicircular Canal (SCC) Dehiscence (Minor et al, 1998), and Benign Paroxysmal Positional Vertigo (BPPV) (Vazquez-Benitez et al, 2016)]. Therapies to prevent damage and to repair or replace damaged tissue will rely on our ability to deliver compounds uniformly and selectively to the inner ear compartments and end organs that require treatment. We cannot adequately design and assess therapeutics if we do not understand how the delivery system impacts drug distribution both within the ear and to the brain and beyond
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