BASIC FIBROBLAST GROWTH-FACTOR (FGF-2) PROTECTS RAT COCHLEAR HAIR-CELLS IN ORGANOTYPICAL CULTURE FROM AMINOGLYCOSIDE INJURY

Given the evidence that basic fibroblast growth factor (FGF-2) can pro tect neural and retinal cells from degeneration, we evaluated the pote ntial of this growth factor to protect sensory cells in the inner ear. When sensory cells of the organ of Corti are exposed to aminoglycosid e antibiotics such as neomycin either in vivo or in vitro, significant ototoxicity is observed. The in vitro cytotoxic effects of neomycin a re dose and time dependent. In neonatal rat organ of Corti cultures, c omplete inner and outer hair cell destruction is observed at high (mM) concentrations of neomycin while inner hair cell survival and severel y damaged outer hair cells are noted at moderate (mu M) concentrations , with a maximal effect observed after 2 days of culture. Approximatel y 50% of cochlear outer hair cells are lost at a dose of 35 mu M neomy cin, and most surviving cells show disorganized stereocilia. Inner hai r cells show primarily disorganization of their stereocilia. A signifi cant protective effect is observed when the organ of Corti is pre-trea ted with FGF-2 (500 ng/ml) for 48 hours, and then FGF-2 is included wi th neomycin in the culture medium. A greater extent of outer hair cell survival and a significant decrease in stereociliary damage are noted with FGF-2. However, disorganization of inner hair cell stereocilia i s unaffected by FGF-2. The protective effect of FGF-2 is specific, sin ce interleukin-1B, nerve growth factor, tumor necrosis factor, and epi dermal growth factor are ineffective, while retinoic acid and transfor ming growth factor alpha show only a moderate protective effect. These results confirm the potential of molecules like FGF-2 for preventing cell death due to a variety of causes. (C) 1996 Wiley-Liss, Inc.