title: Absence of hair cell protection by exogenous FGF-1 and FGF-2 delivered to guinea pig cochlea in vivo.
abstract: Recent findings that glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3), and transforming growth factor a can protect the auditory hair cells from acoustic trauma or aminoglycoside ototoxicity in vivo raise the question of whether other neurotrophic factors can also protect the hair cells in vivo. Fibroblast growth factor-2 (FGF-2) can protect hair cells from neomycin ototoxicity in vitro, and in vivo study has shown upregulation of FGF receptor-3 in the cochlea following noise exposure, suggesting that some FGF family members might play a role in protection or repair of the cochlea from damage. We therefore examined if FGF-1 and FGF-2 chronically delivered to the cochlea prior to noise overstimulation can attenuate noise-induced hair cell damage in vivo under conditions in which GDNF and NT-3 were effective. Pigmented female guinea pigs underwent left scala tympani implantation of a microcannula attached to an osmotic pump filled with artificial perilymph only or containing FGFs (10 or 1 mg/ml FGF-1 or 10 mg/ml FGF-2). They were exposed to noise (4 kHz octave band, 115 dB SPL, 5 hr) 4 days after surgery. Threshold shifts 10 days postexposure were essentially equivalent at all frequencies tested across different treatment groups. No significant difference in threshold shifts was observed between the treated and untreated ears in any of the groups. The extent of hair cell damage was also comparable among the different treatment groups. These findings indicate that exogenous FGF-1 or FGF-2 does not influence noise-induced hair cell damage under the experimental conditions used in this study, suggesting that these FGFs are not good candidates as auditory hair cell protectors in vivo.
authors.affiliation: Kresge Hearing Research Institute, 1301 East Ann Street, Ann Arbor, Michigan 48109-0506, USA.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamasoba
authors.forename: Richard A.
authors.initials: RA
authors.lastname: Altschuler
authors.forename: Yehoash
authors.initials: Y
authors.lastname: Raphael
authors.forename: Amy L.
authors.initials: AL
authors.lastname: Miller
authors.forename: Fumi
authors.initials: F
authors.lastname: Shoji
authors.forename: Josef M.
authors.initials: JM
authors.lastname: Miller