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OBJECTIVE: Recent studies have identified the capacity of transforming growth factor-alpha (TGF-alpha) to stimulate mammalian labyrinthine hair cell regeneration after acute ototoxic damage. Augmenting hair cell regeneration with such growth factors may have a role in potentiation of recovery of cochlear function after hair cell injury. Transtympanic application of aqueous solutions to the round window membrane (RWM) has proved successful as a drug delivery route. The purpose of this study was to test the permeability of the mammalian RWM to TGF-alpha in an inexpensive and reliable in vitro model. METHODS: Guinea pig RWM niches were harvested and transferred to a 2-chamber apparatus, and TGF-alpha was applied to the middle-ear side of the chamber. ELISAs of TGF-alpha were measured at intervals during a 96-hour period. RESULTS: Aliquots taken during a 96-hour interval demonstrated passage of TGF-alpha in concentrations sufficient to stimulate hair cell regrowth. CONCLUSIONS: The apparatus allows study of RWM permeability to other substances and provides a basic model for study of RWM physiology. TGF-alpha is able to pass through a mammalian RWM.
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Witte et al. (2000) studied this question.
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