Transforming growth factor-alpha-induced cellular changes in organotypic cultures of juvenile, amikacin-treated rat organ of Corti

Hair cell losses in the mammalian cochlea following an ototoxic insult are irreversible. However, past studies have shown that amikacin treatment in r at cochleae resulted in the transient presence of atypical Deiters' cells ( ACs) in the damaged organ of Corti. These ACs arise through a transformatio n of Deiters' cells, which produce, at their apical pole, densely packed mi crovilli reminiscent of early-differentiating stereociliary bundles. The AC s do not, however, express typical hair cell markers such as parvalbumin or calbindin. The present study was designed to determine whether specific gr owth factors could influence the survival and differentiation of these ACs and stimulate hair cell regeneration processes in vitro. Apical-medial segm ents of organ of Corti of juvenile amikacin-treated rats were established a s organotypic cultures, and the effects of epidermal growth factor (EGF), i nsulin-like growth factor 1 (IGF-1), transforming growth factor-alpha (TGF alpha), and retinoic acid were studied using morphological and molecular ap proaches. Our results indicate that TGF alpha supports the survival of the damaged organ of Corti and influences ACs differentiation in vitro, possibl y acting through reorganization of the actin cytoskeleton. These effects co uld be directly mediated through activation of the EGF receptor, which is e xpressed by supporting cells in the mature organ of Corti. TGFa does not, h owever, allow the ACs to progress towards a hair cell phenotype. (C) 2002 W iley-Liss, Inc.