Round window membrane permeability to transforming growth factor-alpha: Anin vitro study

OBJECTIVE: Recent studies have identified the capacity of transforming grow th factor-alpha (TGF-alpha) to stimulate mammalian labyrinthine hair cell r egeneration after acute ototoxic damage. Augmenting hair cell regeneration with such growth factors may have a role in potentiation of recovery of coc hlear function after hair cell injury, Transtympanic application of aqueous solutions to the round window membrane (RWM) has proved successful as a dr ug delivery route. The purpose of this study was to test the permeability o f the mammalian RWM to TGF-alpha in an inexpensive and reliable in vitro mo del. METHODS: Guinea pig RWM niches were harvested and transferred to a 2-chambe r apparatus, and TGF-alpha was applied to the middle-ear side of the chambe r. ELISAs of TGF-alpha were measured at intervals during a 96-hour period. RESULTS: Aliquots taken during a Pb-hour interval demonstrated passage of T GF-alpha in concentrations sufficient to stimulate hair cell regrowth, CONCLUSIONS: The apparatus allows study of RWM permeability to other substa nces and provides a basic model for study of RWM physiology. TGF-alpha is a ble to pass through a mammalian RWM.