Basic fibroblast growth factor (FGF-2) protects rat cochlear hair cells in organotypical culture from aminoglycoside injury

Abstract

Given the evidence that basic fibroblast growth factor (FGF-2) can protect neural and retinal cells from degeneration, we evaluated the potential of this growth factor to protect sensory cells in the inner ear. When sensory cells of the organ of Corti are exposed to aminoglycoside antibiotics such as neomycin either in vivo or in vitro, significant ototoxicity is observed. The in vitro cytotoxic effects of neomycin are dose and time dependent. In neonatal rat organ of Corti cultures, complete inner and outer hair cell destruction is observed at high (mM) concentrations of neomycin while inner hair cell survival and severely damaged outer hair cells are noted at moderate (microM) concentrations, with a maximal effect observed after 2 days of culture. Approximately 50% of cochlear outer hair cells are lost at a dose of 35 microM neomycin, and most surviving cells show disorganized stereocilia. Inner hair cells show primarily disorganization of their stereocilia. A significant protective effect is observed when the organ of Corti is pre-treated with FGF-2 (500 ng/ml) for 48 hours, and then FGF-2 is included with 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 is unaffected by FGF-2. The protective effect of FGF-2 is specific, since interleukin-1B, nerve growth factor, tumor necrosis factor, and epidermal growth factor are ineffective, while retinoic acid and transforming 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.

Interactive roles of fibroblast growth factor 2 and neurotrophin 3 in the sequence of migration, process outgrowth, and axonal differentiation of mouse cochlear ganglion cells

“…The presence of FGFs (FGF1 and FGF2) in the brain and their neurite‐promoting effect on various cells reflects an important physiological function in the nervous system (Gospodarowicz, 1987; Ernfors et al, 1990; Matsuyama et al, 1992; Gomez‐Pinilla et al, 1994). In the mammalian inner ear, the FGFs and their receptors have been demonstrated by immunohistochemistry and by in situ hybridization in the neonatal rat (Ernfors et al, 1990; Després et al, 1991; Luo et al, 1993, 1995; Pirvola et al, 1995; Riedel et al, 1995; Low et al, 1996; Dazert et al, 1998; Pickles et al, 1998). We have previously defined a critical period for the influence of FGFs and neurotrophins on the early development of the CG in chick embryos (Hossain et al, 1997).…”

Die Wirkung von Fibroblastenwachstumsfaktor-1 (FGF-1) auf Spiralganglienzellen der Säugetiercochlea

“…Lebenswoche der Ratte konzentrationsund zeitabhängig auf das Wachstumsverhalten kochleärer Haarzellen, Stützzellen und Spiralganglienzellen Einfluß nehmen [2,3,12]. Lebenswoche der Ratte konzentrationsund zeitabhängig auf das Wachstumsverhalten kochleärer Haarzellen, Stützzellen und Spiralganglienzellen Einfluß nehmen [2,3,12].…”

“…Von klinischem Interesse sind die Befunde an Explantaten des Cortischen Organs neugeborener Ratten, an denen sich nach Applikation von FGF-2 eine Protektion äußerer Haarzellen gegenüber einer ototoxischen Schädigung durch Aminoglykosidantibiotika nachweisen ließ [12]. Da äußere Haarzellen gegenüber verschiedenen Schädigungsparametern deutlich empfindlicher reagieren als innere Haarzellen, eröffnen sich hierdurch mögliche Behandlungsstrategien zum Hörerhalt gefährdeter Patienten.…”

“…Nach Haarzelluntergang kommt es u.a. Lebenswoche der Ratte konzentrationsund zeitabhängig auf das Wachstumsverhalten kochleärer Haarzellen, Stützzellen und Spiralganglienzellen Einfluß nehmen [2,3,12]. Da Patienten mit einer haarzellbedingten Schwerhörigkeit, aber intaktem neuronalen System, potentiell mit einem "cochlear implant" versorgt werden können, kommt dem Erhalt der Spiralganglienzellen eine besondere Bedeutung zu.…”

Growth factors have a protective effect on neomycin‐induced hair cell loss

“…Both EGF and TGF‐a stimulated the hair cell replacement after aminoglycoside ototoxic trauma in rat cochlear organotypic culture (Zine and de Ribaupierre, ). Growth factors may be involved in protection and regeneration of the mammalian inner ear, such as FGF‐2 alone (Zhai et al, ), combination retinoic acid (RA) and TGF‐α (Malgrange et al, ), or combination RA and FGF‐2 (Low et al, ).…”