Hearing Preservation Following Repeated Adenovector Delivery

• Published in: Anatomical record (Hoboken, N.J. : 2007) Vol. 303; no. 3; pp. 600 - 607
• Main Authors: Pfannenstiel, Susanna C., Praetorius, Mark, Brough, Douglas E., Staecker, Hinrich
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.03.2020; Wiley Subscription Services, Inc
• Subjects: ABR; adenovector; Animals; Auditory system; Brain stem; cochlea; DPOAE; Drug Administration Routes; Ear, Inner - physiology; Evoked Potentials, Auditory, Brain Stem - physiology; Female; gene therapy; Genetic Vectors; Hearing - physiology; Hearing loss; Inflammation; Inner ear; Mice; Otoacoustic emissions; Preservation; Semicircular canals; Surgery; adenovector; ABR; cochlea; DPOAE; gene therapy; hearing loss; mice
• ISSN: 1932-8486; 1932-8494
• DOI: 10.1002/ar.24347

ABSTRACT Factors influencing the damage to the inner ear can include the surgical approach used for vector delivery, the volume of vector used, the buffer that the vector is suspended in as well as the host response to the vector capsid and vector genes that are transferred. We evaluated the effect of Ad5 capsid adenovectors on hearing function after delivery to the perilymph of adult C57Bl/6 mice. Hearing was evaluated before surgery and 3 days post‐surgery by auditory brain stem response (ABR) and distortion product otoacoustic emissions (DPOAE). A second group of mice underwent repeated delivery of adenovector two times to determine if a preliminary exposure to an Ad vector could induce an inflammatory response leading to further loss. The first adenovector (Ad.11D.LacZ) was delivered to the posterior semicircular canal or via round window. In the second surgery, a second adenovector (Ad.11D.gfp) was delivered to the horizontal semicircular canal. The functional outcome was tested prior, 7 days post first vector delivery, and 3 days post second vector delivery via ABR and DPOAE. Dual delivery via the semicircular canals resulted in preservation of hearing suggesting that pre‐exposure to Ad5 capsid does not predispose to hearing loss. Delivery to the round window resulted in hearing loss that was worsened after the second vector delivery, suggesting that delivery route and prior injury to the inner ear rather than the repetition of delivery predisposes to further hearing loss. Anat Rec, 303:600–607, 2020. © 2019 American Association for Anatomy