Destruction of hair cells in the human ear results in irreversible loss of equilibrium or hearing sensitivity since our ears do not produce hair cells after birth. Recently, as an NIH Postdoctoral Fellow I demonstrated hair cell production occurring perpetually in the ears of sharks and rays. This results in the addition of new hair cells equal to 5 times the number in the human organ of Corti and is accompanied by a 500-fold increase in physiological sensitivity. In these ears, due to the persistence of hair cell production, hair cell damage may be reversible through regeneration at any age. Here in my first application for an NIH research grant I outline a plan to continue investigating this sensory epithelium growth and to test the regenerative abilities of perpetually growing ears. Ototoxic antibiotics and cryogenic surgery will be used to damage hair cells, then scanning EM will be used to evaluate the ear's ability to generate new hair cells. Regional rates of hair cell production and suspected links between hair cell age and ultrastructure will be measured with microautoradiography. Intracellular staining will be used to describe how terminal branches of statoacoustic neurons expand to contact epithelia that are increasing by thousands of hair cells per year. The regenerative capacity of peripheral statoacoustic neurites and the mechanisms that guide the perpetual growth of these terminals will be studied by denervating growing epithelia. Physiological response changes associated with growth will be investigated further by recording individually from neurons that contact large hair cells, and from others that contact smaller, apparently younger hair cells at the outer edges of growing epithelia. The characteristics of growing hair cell epithelia are common to many forms, including the embryonically developing ears of mammals and the perpetually growing ears of elasmobranchs. The information sought here is essential to understanding the limits and capacities of regeneration and self repair in hair cell epithelia. It pertains directly to possible recovery from sensory-neural hearing loss and balance disorders and to the development of normal and abnormal function in human ears.
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