title: Atoh1 induces auditory hair cell recovery in mice after ototoxic injury.
abstract: OBJECTIVE
  To evaluate the ability of the Ad28.gfap.atoh1 to promote hair cell regeneration and hearing recovery in cochlea injured with kanamycin and furosemide.
  
  
  METHODS
  In vivo model of hair cell ablation and subsequent treatment with Atoh1.
  
  
  METHODS
  The hair cells of C57BL/6 mice were ablated with systemic administration of kanamycin and furosemide. The left ears were treated with Ad28.gfap.atoh1. The right ears were not treated. Preablation audiograms and distortion product otoacoustic emissions (DPOAEs) were compared to 1- or 2-month postablation studies. Harvested cochleae were examined for histologic evidence of hair cell regeneration and spiral ganglion cell survival.
  
  
  RESULTS
  Delivery of Ad28.gfap.atoh1 results in development of auditory hair cells. There was no recovery of DPOAEs at 1 or 2 months post-treatment. Two months after delivery of Ad28.gfap.atoh1, the left ear exhibited a moderate recovery of hearing at 4 and 8 kHz (P < .01). There was no significant difference at 16 or 32 kHz. One month after treatment, myosin VII-positive immunohistochemical staining can be seen in both the inner and outer hair cells of the treated ear. In the untreated ear, minimal myosin VII-positive debris is seen, with no indication of normal hair cells. Two months after ablation, there is evidence of hair cell recovery on the treated side, whereas the untreated cochlea demonstrates a flattened epithelium. Untreated ears showed decreased spiral ganglion cell density at the basal turn compared to treated ears.
  
  
  CONCLUSIONS
  Ad28.gfap.atoh1 promotes hair cell regeneration in cochlea ablated with kanamycin and furosemide resulting in moderate hearing recovery.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Kansas School of Medicine, Kansas City, Kansas 66160, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Kraft
authors.forename: Chi
authors.initials: C
authors.lastname: Hsu
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Brough
authors.forename: Hinrich
authors.initials: H
authors.lastname: Staecker
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D051792:Basic Helix-Loop-Helix Proteins / Q000627:therapeutic use*; D015834:Cochlear Diseases / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D004232:Diuretics / Q000009:adverse effects*; D005665:Furosemide / Q000009:adverse effects*; D015316:Genetic Therapy; D006198:Hair Cells, Auditory / Q000473:pathology*; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000628:therapy*; D007612:Kanamycin / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D012038:Regeneration
chemical_list: D000900:Anti-Bacterial Agents; D051792:Basic Helix-Loop-Helix Proteins; D004232:Diuretics; D005665:Furosemide; D007612:Kanamycin; C500943:Atoh1 protein, mouse