| Hair cells are the specialized sensory epithelial cells in the inner ear. Loss of or damage to hair cells, such as due to acoustic overstimulation or aminoglycoside antibiotics, results in auditory or vestibular deficit. In many species, the loss of hair cells is followed by proliferative regeneration of new hair cells bringing about morphological and functional recovery. In mammals, however, there is little proliferative regeneration and sensory dysfunction due to loss of hair cells is largely permanent. The work herein explores several aspects of repair and regeneration in the inner ear.; The first series of experiments describe a method for labeling hair cells by permeation of a fluorescent dye, FM1--43, through their mechanosensory transduction channels. Further, it demonstrates that similar permeation through sensory channels can occur in a number of cell types, including muscle stretch receptors, nociceptors, taste receptors and taste receptive fibers, enteric stretch receptors, and Merkel cells in whisker vibrissae, hair follicles, and touch domes. The second series of experiments find that isolated, but innervated and apparently functional, hair cells are capable of surviving in the extra-macular epithelium that surrounds the sensory macula in the bullfrog saccule. The third series of experiments demonstrate that hair cells can pinch off their hair bundles following low-dose aminoglycoside antibiotic intoxication, and survive as bundleless cells. Within a week, the number of cells with hair bundles increases, and some hair cells that lost part of their hair bundle develop a new hair bundle next to the remnant of their old bundle, demonstrating that hair cells are capable of repair following ototoxic damage. The final series of experiments demonstrate that shape change is a critical trigger for initiation of proliferation in mammalian supporting cells, but that shape change in vitro or in situ is inhibited in mature supporting cells. Furthermore, stimulation of shape change during wound closure in situ is sufficient to reverse supporting cell quiescence, even in mature epithelia. Together, these results provide insight into several aspects of inner ear function and regeneration, in particular suggesting methods that may lead to initiation of regeneration in the mammalian inner ear. |
