Dye Tracking Following Posterior Semicircular Canal or Round Window Membrane Injections Suggests a Role for the Cochlea Aqueduct in Modulating Distribution

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.

Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear Implants

“…This might increase the transduction rate while securing SGN survival. Approaches reported in the literature mostly aimed at administration to the perilymphatic space, combining, for example, round window injection with posterior semicircular canal fenestration (PSCC) or injection from the PSCC to the round window ( Yoshimura et al, 2018 ; Talaei et al, 2019 ).…”

The DNA methylation inhibitor RG108 protects against noise-induced hearing loss

“…Yoshimura et al described RWM injection with semicircular canal fenestration in PSCC as a safe technique for cochlear gene therapy (Yoshimura et al 2018). A study by Talaei et al reported that PSCC injection induces higher levels of dye delivery within neonatal and adult mice cochleae compared with RWM injections (Talaei et al 2019). Additionally, a technical shortcoming of PSCC injection is that it remains uncertain whether the injected therapeutic agent is administered into the endolymph or perilymph (Kawamoto et al 2001).…”

Transduction Efficiency and Immunogenicity of Viral Vectors for Cochlear Gene Therapy: A Systematic Review of Preclinical Animal Studies

“…The posterior semicircular approach (PSC) is used to access the vestibular organs, but is also capable of accessing the cochlea. A significant limitation of the PSC approach is the difficulty to determine whether the vector is injected into the endolymph or perilymph (Talaei et al, 2019 ). However, because of its relatively easy accessibility, the risk of surgical trauma and thus inner ear damage is decreased, which makes PSC an interesting delivery method (Isgrig and Chien, 2018 ; Ji et al, 2019 ).…”