Adenovirus-mediated overexpression of a gene prevents hearing loss and progressive inner hair cell loss after transient cochlear ischemia in gerbils

N. Hakuba, K. Watabe, J. Hyodo, T. Ohashi, Y. Eto, M. Taniguchi, L. Yang, J. Tanaka, Ryuji Hata, K. Gyo

Research output: Contribution to journalReview article

41 Citations (Scopus)

Abstract

The use of adenoviral vectors has recently provided a novel strategy for direct gene transfer into the cochlea. In this study, we assessed the utility of an adenoviral vector expressing glial-cell-derived neurotrophic factor (GDNF) in ischemia-reperfusion injury of the gerbil cochlea. The vector was injected through the round window 4 days before ischemic insult. The distribution of a reporter transgene was confirmed throughout the cochlea from the basal to the apical turn and Western blot analysis indicated significant upregulation of GDNF protein 11 days following virus inoculation. Hearing ability was assessed by sequentially recording compound action potentials (CAP), and the degree of hair cell loss in the organ of Corti was evaluated in specimens stained with rhodamine-phalloidin and Hoechst 33342. On the seventh day of ischemia, the CAP threshold shift and inner hair cell loss were remarkably suppressed in the Ad-GDNF group compared with the control group. These results suggest that adenovirus-mediated overexpression of GDNF is useful for protection against hair cell damage, which otherwise eventually occurs after transient ischemia of the cochlea.

Original languageEnglish
Pages (from-to)426-433
Number of pages8
JournalGene therapy
Volume10
Issue number5
DOIs
Publication statusPublished - 01-03-2003

Fingerprint

Inner Auditory Hair Cells
Gerbillinae
Cochlea
Alopecia
Nerve Growth Factors
Hearing Loss
Adenoviridae
Ischemia
Neuroglia
Genes
Action Potentials
Organ of Corti
Aptitude
Reperfusion Injury
Transgenes
Hearing
Up-Regulation
Western Blotting
Viruses
Control Groups

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Hakuba, N. ; Watabe, K. ; Hyodo, J. ; Ohashi, T. ; Eto, Y. ; Taniguchi, M. ; Yang, L. ; Tanaka, J. ; Hata, Ryuji ; Gyo, K. / Adenovirus-mediated overexpression of a gene prevents hearing loss and progressive inner hair cell loss after transient cochlear ischemia in gerbils. In: Gene therapy. 2003 ; Vol. 10, No. 5. pp. 426-433.
@article{6a9ddd27f8de4191a2eaf5c4a5291583,
title = "Adenovirus-mediated overexpression of a gene prevents hearing loss and progressive inner hair cell loss after transient cochlear ischemia in gerbils",
abstract = "The use of adenoviral vectors has recently provided a novel strategy for direct gene transfer into the cochlea. In this study, we assessed the utility of an adenoviral vector expressing glial-cell-derived neurotrophic factor (GDNF) in ischemia-reperfusion injury of the gerbil cochlea. The vector was injected through the round window 4 days before ischemic insult. The distribution of a reporter transgene was confirmed throughout the cochlea from the basal to the apical turn and Western blot analysis indicated significant upregulation of GDNF protein 11 days following virus inoculation. Hearing ability was assessed by sequentially recording compound action potentials (CAP), and the degree of hair cell loss in the organ of Corti was evaluated in specimens stained with rhodamine-phalloidin and Hoechst 33342. On the seventh day of ischemia, the CAP threshold shift and inner hair cell loss were remarkably suppressed in the Ad-GDNF group compared with the control group. These results suggest that adenovirus-mediated overexpression of GDNF is useful for protection against hair cell damage, which otherwise eventually occurs after transient ischemia of the cochlea.",
author = "N. Hakuba and K. Watabe and J. Hyodo and T. Ohashi and Y. Eto and M. Taniguchi and L. Yang and J. Tanaka and Ryuji Hata and K. Gyo",
year = "2003",
month = "3",
day = "1",
doi = "10.1038/sj.gt.3301917",
language = "English",
volume = "10",
pages = "426--433",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",
number = "5",

}

Adenovirus-mediated overexpression of a gene prevents hearing loss and progressive inner hair cell loss after transient cochlear ischemia in gerbils. / Hakuba, N.; Watabe, K.; Hyodo, J.; Ohashi, T.; Eto, Y.; Taniguchi, M.; Yang, L.; Tanaka, J.; Hata, Ryuji; Gyo, K.

In: Gene therapy, Vol. 10, No. 5, 01.03.2003, p. 426-433.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Adenovirus-mediated overexpression of a gene prevents hearing loss and progressive inner hair cell loss after transient cochlear ischemia in gerbils

AU - Hakuba, N.

AU - Watabe, K.

AU - Hyodo, J.

AU - Ohashi, T.

AU - Eto, Y.

AU - Taniguchi, M.

AU - Yang, L.

AU - Tanaka, J.

AU - Hata, Ryuji

AU - Gyo, K.

PY - 2003/3/1

Y1 - 2003/3/1

N2 - The use of adenoviral vectors has recently provided a novel strategy for direct gene transfer into the cochlea. In this study, we assessed the utility of an adenoviral vector expressing glial-cell-derived neurotrophic factor (GDNF) in ischemia-reperfusion injury of the gerbil cochlea. The vector was injected through the round window 4 days before ischemic insult. The distribution of a reporter transgene was confirmed throughout the cochlea from the basal to the apical turn and Western blot analysis indicated significant upregulation of GDNF protein 11 days following virus inoculation. Hearing ability was assessed by sequentially recording compound action potentials (CAP), and the degree of hair cell loss in the organ of Corti was evaluated in specimens stained with rhodamine-phalloidin and Hoechst 33342. On the seventh day of ischemia, the CAP threshold shift and inner hair cell loss were remarkably suppressed in the Ad-GDNF group compared with the control group. These results suggest that adenovirus-mediated overexpression of GDNF is useful for protection against hair cell damage, which otherwise eventually occurs after transient ischemia of the cochlea.

AB - The use of adenoviral vectors has recently provided a novel strategy for direct gene transfer into the cochlea. In this study, we assessed the utility of an adenoviral vector expressing glial-cell-derived neurotrophic factor (GDNF) in ischemia-reperfusion injury of the gerbil cochlea. The vector was injected through the round window 4 days before ischemic insult. The distribution of a reporter transgene was confirmed throughout the cochlea from the basal to the apical turn and Western blot analysis indicated significant upregulation of GDNF protein 11 days following virus inoculation. Hearing ability was assessed by sequentially recording compound action potentials (CAP), and the degree of hair cell loss in the organ of Corti was evaluated in specimens stained with rhodamine-phalloidin and Hoechst 33342. On the seventh day of ischemia, the CAP threshold shift and inner hair cell loss were remarkably suppressed in the Ad-GDNF group compared with the control group. These results suggest that adenovirus-mediated overexpression of GDNF is useful for protection against hair cell damage, which otherwise eventually occurs after transient ischemia of the cochlea.

UR - http://www.scopus.com/inward/record.url?scp=0037347806&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037347806&partnerID=8YFLogxK

U2 - 10.1038/sj.gt.3301917

DO - 10.1038/sj.gt.3301917

M3 - Review article

C2 - 12601397

AN - SCOPUS:0037347806

VL - 10

SP - 426

EP - 433

JO - Gene Therapy

JF - Gene Therapy

SN - 0969-7128

IS - 5

ER -