Hearing Preservation Following Repeated Adenovector Delivery.
ABR
DPOAE
adenovector
cochlea
gene therapy
hearing loss
mice
Journal
Anatomical record (Hoboken, N.J. : 2007)
ISSN: 1932-8494
Titre abrégé: Anat Rec (Hoboken)
Pays: United States
ID NLM: 101292775
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
04
12
2019
accepted:
06
12
2019
pubmed:
10
1
2020
medline:
28
1
2021
entrez:
10
1
2020
Statut:
ppublish
Résumé
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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
600-607Informations de copyright
© 2020 American Association for Anatomy.
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