Researchers have discovered that deletion of a specific gene permits the proliferation of new hair cells in the cochlea of the inner ear -- a finding that offers promise for treatment of age-related hearing loss. This type of hearing loss is caused by aging, disease, certain drugs, and the cacophony of modern life. It is the most common cause of hearing loss in older people.
The research team, which included Howard Hughes Medical Institute investigator David P. Corey, published their findings on January 13, 2005, in Science Express, which provides rapid electronic publication of selected Science publications. Zheng-Yi Chen, who is at Massachusetts General Hospital and Harvard Medical School, is the senior author of the article. He trained with Corey at Harvard Medical School. Other co-authors are from the University of Virginia School of Medicine, Tufts-New England Medical Center, and Northwestern University.
Hair cells in the cochlea detect sound by vibrating in response to sound waves, triggering nerve impulses that travel to the auditory region of the brain. Normally, humans are born with a complement of about 50,000 hair cells. But since the cells do not regenerate, the steady rate of hair-cell loss that can accompany aging produces significant hearing loss in about a third of the population by the time they reach 70-years-old.
Chen did a broad survey that examined patterns of gene expression during embryonic development of the balance organ of the inner ear. His results suggested that there might be a gene that produces a protein that acts as a permanent "brake" on hair-cell regeneration. That survey, which was done in mice, revealed that the retinoblastoma gene seemed to be particularly active during embryonic development.
At the same time, co-author Philip Hinds at Tufts-New England Medical Center had developed a knockout mouse lacking the retinoblastoma gene Rb1.
"He noticed that these mice ran in circles, and for an inner-ear biologist, a mouse running in circles immediately tells you that there is some problem with the vestibular system of the inner ear," said Corey. Thus, he said, Chen began a detailed study of the hair cells of the knockout mice. Those studies revealed that the mice without Rb1 had more hair cells than normal mice, and the cells were actively proliferating.
Corey and his colleagues then launched studies to determine whether the proliferating cells were, indeed, functional hair cells. They found that mechanically stimulating the cells generated an electrical signal characteristic of hair cells. Also, Corey and his colleagues found that the cells absorbed a fluorescent dye that only moves through the membrane channels of functional hair cells.