Aims: Methionine sulfoxide reductase B3 (MsrB3), which stereospecifically repairs methionine- R -sulfoxide, is an important Msr protein that is associated with auditory function in mammals. MsrB3 deficiency leads to profound congenital hearing loss due to the degeneration of stereociliary bundles and the apoptotic death of cochlear hair cells. In this study, we investigated a fundamental treatment strategy in an MsrB3 deficiency mouse model and confirmed the biological significance of MsrB3 in the inner ear using MsrB3 knockout (
MsrB3
−/− ) mice. Results: We delivered a recombinant adeno-associated virus encoding the MsrB3 gene directly into the otocyst at embryonic day 12.5 using a transuterine approach. We observed hearing recovery in the treated ears of
MsrB3
−/− mice at postnatal day 28, and we confirmed MsrB3 mRNA and protein expression in cochlear extracts. Additionally, we demonstrated that the morphology of the stereociliary bundles in the rescued ears of
MsrB3
−/− mice was similar to those in
MsrB3
+/+ mice. Innovation: To our knowledge, this is the first study to demonstrate functional and morphological rescue of the hair cells of the inner ear in the MsrB3 deficiency mouse model of congenital genetic sensorineural hearing loss using an in utero , virus-mediated gene therapy approach. Conclusion: Our results provide insight into the role of MsrB3 in hearing function and bring us one step closer to hearing restoration as a fundamental therapy. Antioxid. Redox Signal. 24, 590–602.
5 January 2017 in ACS Applied Materials & Interfaces
We describe the design and development of a tri-coil bellows transducer (TCBT) for use in an implantable middle-ear hearing aid for round window (RW) drive. The TCBT provides easy implantation and a better frequency response than previous RW middle-ear transducers. It consisted of three cylindrical coils, a bonded magnet, and a tiny bellows with multiple corrugations. The simulation started with the calculation of the vibrational force required for the RW-drive transducer. Based on the anatomical structure of the RW niche and its volume, the designed TCBT was 1.75 mm in diameter and 2.3 mm long. To maximize the electromagnetic force of a TCBT installed within the limited volume of the RW niche, its structure was designed using an electromagnetic analysis based on finite-element analysis to determine the each length of the three cylindrical coils and the bonded magnet inside the TCBT. Additionally, the resonance frequency characteristics of the TCBT were determined using mechanical vibration analysis. A prototype TCBT was fabricated according to the simulation results, and an experiment to evaluate its vibrational characteristics was performed with the TCBT in an unloaded condition. Finally, the performance of the TCBT for use in RW-drive implantable middle-ear hearing aids was confirmed in experiments with cadaveric temporal bones.