Jeffrey T. Corwin, Ph.D.
Ph.D., 1980, University of California, San Diego
REGENERATION OF AUDITORY RECEPTOR CELLS
The permanence of neuronal loss makes deafness, blindness, stroke, Alzheimer's disease, and other neurological disorders so devastating, but in some vertebrate species injury to the nervous system is followed by dramatic recovery of function. We are investigating mechanisms for preventing loss of neurosensory cells and mechanisms for regenerating replacements after loss.
Over 17 million Americans have significant hearing deficits from loss of sensory hair cells, the acoustic receptors in the ear. Those losses have been considered permanent in humans, but that is not the case in other species. Sharks and other "cold-blooded" vertebrates add sensory cells to their auditory detectors throughout life, and the auditory detectors in the ears of birds, members of a "warm blooded" class, are regenerated on demand, leading to recovery from kinds of deafness and balance disorders that are permanent when they occur in humans. We were recently encouraged to discover that sensory hair cells can be repaired or regenerated in the balance organs of mammals, even though that occurs at a low rate. Our current work stems from that discovery.
Those discoveries have allowed us to begin to identify the triggers which control cell replacement in that part of the nervous system. In addition, our work has expanded with the discovery of a growth factor treatment that protects hair cells from drugs that normally cause their death. Cell and organ culture, immunocytochemistry, molecular biology, time-lapse video microscopy, laser microbeam cell surgery, eletrophoresis, scanning and transmission electron microscopy, electrophysiology, intracellular injections, and microsurgical methods are used in our investigations in projects involving chicks, mice, guinea pigs, human tissues, salamanders, and sharks. Working with biotechnology companies we have identified growth factors that promote the regenerative process and we are seeking others which may further enhance the low level of cell regeneration that can occur in mammals. Successful results could significantly improve the quality of life for many people who have sensorineural hearing losses and balance disorders that are currently considered irreversible. In addition, studies of the relatively simple and defined neurosensory structures of the ear may lead to information that could be useful in attempts to regenerate other elements of the nervous system.
Funding sources: National Institutes of
Health, Lions of Virginia Hearing Foundation, Deafness Research
Foundation, National Organization for Hearing Research.
PubMed Link to Corwin Publications
TOP LEFT: A micrograph of a sensory hair cell taken at the moment when the laser microbeam "zapped" the cell, producing a small black spot (arrow) within the circular outline of its nucleus. TOP RIGHT: A microscopic image of a dividing cell that is part of the proliferative response evoked by the death of adjacent sensory hair cells.
BOTTOM: A scanning electron microscope view of the forming hair cell bundles of replacement sensory cells, which developed after renewed cell proliferation in the damaged hearing organ of a bird.
- Forge, A., Li, L., Corwin, J., and Nevill, G. (1993) Ultrastructural evidence for hair cell regeneration in the mammalian inner ear. Science 259:1616-1619.
- Warchol, M., Lambert, P., Goldstein, B., Forge, A., and Corwin, J. (1993) Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans. Science 259:1619-1622.
- Kelley, M., Xu, X., Wagner, M., Warchol, M., and Corwin, J. (1993) The developing organ of cortin contains retinoic acid and forms supernumerary hair cells in response to exogenous retinoic acid in culture. Development 119:1041-1053.
- Warchol, M. and Corwin, J. (1993) Supporting cells in avian vestibular organs proliferate in serum-free culture. Hear Res. 71:28-36.
- Kelley, M., Talreja, D. and Corwin, J. (1995) Replacement of haircells after laser microbeam irradiation in cultured organs of Corti from embryonic neonatal mice. J. Neurosci. 15:3013-3026.
- Warchol, M. and Corwin, J. (1996) Regenerative proliferation in organ cultures of the avian cochlea: Identification of the initial progenitors and determination of the latency of the proliferative response. J. Neurosci. 16: 5466-5477.
- Jones, J. and Corwin, J. (1996) Regeneration of sensory cells after laser ablation in the lateral line system: Hair cell lineage and macrophage behavior revealed by time-lapse video microscopy. J. Neurosci. 16: 649-662.
- Saffer, L., Gu, R. and Corwin, J. (1996) An RT-PCR analysis of mRNA for growth factor receptors in damaged and control sensory epithelia of rat utricles. Hearing Res. 94: 14-23.
- Corwin, J., Warchol, M., Saffer, L., Finley, J., Gu, R., and Lambert, P. (1996) Growth factors as potential drugs for the sensory epithelia of the ear. In: Growth factors as drugs for neurological and sensory disorders. Ciba Foundation Symposium 1996. John Wiley and Sons, Chichester (pp. 167-187).