The injured avian auditory epithelium can regenerate by replacing lost hair cells. In contrast, loss of hair cells in the mammalian organ of Corti is irreversible. We propose to use a comparative approach to determine why acoustic trauma in mammals results in a scar, whereas in chicks new hair cells are generated. We hypothesize that early responses to acoustic trauma in the organ of Corti are similar to those in the avian basilar papilla. The first two aims will test this hypothesis, using electron microscopy, immunocytochemistry and DNA-specific tracers. We will identify changes in surface morphology, cytoskeletal organization and intercellular junctions which occur during hair cell degeneration and scar formation in noise-exposed chick basilar papillae. We will then compare these parameters in the chick with those in the mammalian organ of Corti.
The third aim will test the hypothesis that generation of new hair cells in chicks is dependent on loss of hair cells and formation of scars. Preliminary evidence that chick supporting cells divide after trauma focused our interest on the responses of supporting cells and the interaction between supporting cells and damaged hair cells. Markers for DNA and proliferation will be applied together with markers for junctional and cytoskeletal proteins to identify changes associated with supporting cell proliferation. Elucidating the spatial and temporal changes which precede supporting cell divisions may help determine the point of divergence at which avian inner ears begin the regenerative process whereas mammals do not. This work pertains to biological mechanisms of tissue healing in general, and to the repair of mosaic epithelial sheets in particular. Elucidating the mechanism of scar formation in the mammalian cochlea may help develop methods to clinically reduce susceptibility to acoustic trauma. Knowledge of the spatial and temporal patterns of scar formation and regeneration in chicks and scar formation in mammals may be useful in developing clinical means to induce generation of new hair cells in humans. Future efforts to unveil a method for inducing mammalian hair cell regeneration will likely focus on the point of divergence, in time and space, where chicks regenerate new hair cells and mammals do not.
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