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Age-Related Hearing Loss May Find A Solution
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An old family photograph from the collection
of investigator David P. Corey demonstrates a method that was
used to compensate for age-related hearing loss. In the
photograph, which was taken around 1910, the young girl, who is
Corey's grandmother, uses a speaking tube to communicate with
Corey's great-great-grandfather. |
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Jan. 25, 2005 Age-related hearing loss, caused by
the loss of hair cells in the inner ear, may find a solution in the
deletion of a specific gene, which researchers say permits the
proliferation of new hair cells in the cochlea. This is the most common
cause of hearing loss for senior citizens and can be caused by aging,
disease, certain drugs, and the jarring sounds of modern life.
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.
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.
This work gives us an invaluable window into the control mechanism,
which could lead to eventual clinical application in regenerating lost
hair cells.
David P. Corey
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.
In further studies, Chen and his colleagues found
that knocking out the Rb1 gene in cultured mature inner ear cells
from mice triggered the cells to begin proliferating.
This experiment demonstrated that it was a direct
effect of the Rb gene and not some indirect effect during
development that controlled proliferation of hair cells, said Corey.
So Zheng-Yi has found that deletion of this gene can allow functioning
hair cells to continue to divide. They are no longer limited by whatever
growth controls existed before. This work gives us an invaluable window
into the control mechanism, which could lead to eventual clinical
application in regenerating lost hair cells, said Corey.
According to Corey, the findings also have
important implications for basic research. A major obstacle to
hair-cell research has been that, since there are not very many hair
cells in the inner ear, it has been hard to get enough material for
study, he said. But with Zheng-Yi's work, we now have the potential
for generating cultured lines of hair cells for experiments.
While we are very excited about the potential for
hair-cell regeneration from this work, much basic research needs to be
done, emphasized Corey. Simply inactivating the Rb gene allows
the hair cells to keep dividing and dividing, which might produce tumors
in the inner ear. So, Zheng-Yi and his colleagues will be seeking ways
to inactivate the gene only long enough to allow a clinically useful
amount of proliferation, before turning the gene back on. The approach,
he said, will require a greater understanding of the mechanisms
controlling the Rb signaling pathway.
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