Archives
Studying how we hear; why we don't
The Center for Hearing and Deafness at UB conducting groundbreaking research
By LOIS BAKER
Contributing Editor
Twenty-eight million Americans—nearly 10 percent of the U.S. population—have lost the ability to hear clearly. As the baby-boom bulge passes into seniorhood and the current elderly population lives longer, that percentage is destined to increase significantly.
Some of the newest research into how we hear and what happens when we don't is being conducted at The Center for Hearing and Deafness at UB, which was established in 1995 by Richard Salvi and Donald Henderson, accomplished researchers who came to UB in 1987 from the University of Texas at Dallas.
Investigators in The Center for Hearing and Deafness include (clockwise from front) Richard Salvi, Donald Henderson, Robert F. Burkhard and Sandra L. McFadden. In 1999, this group was awarded a $5.7 million program project grant from the National Institutes of Health.
PHOTO: K C KRATT
In this multidisciplinary laboratory, specialists in a variety of disciplines are conducting studies in hair cell regeneration, drug therapy and ototoxic drugs, noise-induced hearing loss, middle ear disease, infant hearing loss, central auditory system plasticity, mechanical transduction (the fundamental process of transferring sound energy to electrical energy), age-related hearing loss, hormonal influence on hearing loss and central auditory processing in the brain.
Center scientists have generated more than $12 million in research funding, including a highly competitive $5.7 million multidisciplinary program project grant from the National Institutes of Health that focuses specifically on the mechanisms underlying acquired hearing loss.
Why is a large segment of the population becoming "hard of hearing"?
About 10 million can attribute their loss of hearing to noise exposure. Listening to music through stereo headphones at top volume, for example, is as damaging to the auditory system as the thunder of a diesel locomotive. Thirty million people in the U.S. are exposed to similarly dangerous noise levels each day.
Infections and some cancer chemotherapy drugs also can cause deafness, but the major culprit is Father Time. The National Institute on Deafness and Other Communicative Disorders estimates that 30-35 percent of people between the ages of 65 and 75 have a hearing loss. The percentage climbs to nearly 50 percent among those over 75.
Salvi, professor of communicative disorders and sciences, neurology and otolaryngology, and director of the center, says that until the past five to eight years, people looked at hearing loss from a descriptive point of view. "They measured loss; how poor people were at detecting speech and other sounds, and how well they could hear in a background of noise," he says. "That's been the situation for basically the past 100 years."
Only within the past two decades have hearing researchers begun to understand that hearing depends primarily on the ability of tiny cilia on hair cells of the inner ear to transform sound-wave energy into electrical energy, and on how accurately the brain receives and translates the resulting nerve impulses.
"The big change came with advances in biology and our ability to study how inner ear hair cells develop, live and die," Salvi says. "A huge amount of work is now being done in that area and our lab was one of the first to get involved. Hearing research has moved from the cellular to the molecular level to the genetic level."
Center scientists are responsible for several major advances in the field:
Discovered several classes of compounds that may protect against noise-induced hearing loss
Found a site in the brain associated with the ringing in the ears that affects up to 50 million people in the U.S alone.
Discovered the existence of the so-called "line busy" signal in the inner ear, a phenomenon that leads to significant hearing loss in a manner unrelated to that caused by damage to the ear's sensory cells.
Identified a protective function of the efferent system within the auditory system that affects the development of noise-induced hearing loss
Completed ground-breaking studies in brain plasticity and antioxidant enzyme research
Made major advances in understanding how inner ear hair cells can regenerate in certain birds, raising the possibility that hearing eventually can be restored in humans
Is one of the first laboratories to conduct gene expression studies to determine the cell signaling pathways involved in noise-induced hearing loss
Discovered that toxic free radicals may be a common cause of hearing loss from aging, ototoxic drugs and noise exposure
The center supports eight full-time researchers, approximately 10 doctoral students, six to eight postdoctoral fellows and several visiting scientists, and collaborates with investigators at research centers in Europe and China, several universities in the U.S. and the National Institutes of Health.
Tracing the path of cell death
Most cases of hearing loss occur when inner-ear hair cells in the cochlea are damaged or killed. Hair cells transfer their neural activity to the auditory nerve, which carries the nerve impulses to the brain's central auditory system. Considerable research in recent years has been devoted to finding compounds that might protect against hearing loss by preventing hair cell death or by rescuing and repairing damaged cells.
Center researchers, collaborating with colleagues at Roswell Park Cancer Institute, were among the first to study the process of hair cell death—specifically programmed cell death called apoptosis—in inner-ear hair cells. Salvi and center scientists are attempting to determine what triggers the cell-death switch of apoptosis by subjecting cultured inner-ear sensory cells and sensory neurons to known ototoxic drugs—the antibiotic gentamicin and cancer therapy drugs cisplatin or carboplatin—and tracking the biochemical pathways involved in cell death.
Armed with these findings, the researchers now are using certain drugs to try to block these pathways. The primary candidates are a protease inhibitor called leupeptin and an inhibitor of the tumor suppressor gene P53, which acts as a cell executioner, of sorts.
"Gentamicin is used in the U.S. to treat infections that arise in persons with muscular dystrophy and cystic fibrosis and is used extensively in other parts of the world to treat a wide range of bacterial infections, Salvi says. "Unfortunately, gentamicin causes severe deafness.
"We have found that leupeptin does a tremendous job of rescuing cells exposed to gentamicin. In inner-ear cultures, we see 70 percent loss of hair cells without it, but with it we can rescue most of those cells. We've also shown that using a P53 inhibitor, we can block cisplatin toxicity in the inner ear."
Hair-cell death due to noise exposure is the primary focus of the work of Donald Henderson, professor of communicative disorders and sciences and otolaryngology. He and colleagues are conducting front-line investigations into compounds that may protect the auditory system from too much noise.
They have identified and are concentrating on a family of enzymes, some of which trigger the death process and some which execute it. "Now, we are trying to trace the pathway of these enzymes to their starting point," says Henderson. "If we can do this, we can rescue, and perhaps prevent, hearing loss due to noise damage."
The role of genes
Hearing loss due to aging, responsible for the largest cohort of the hearing impaired, also may have a genetic component, an avenue Robert F. Burkard, professor of communicative disorders and sciences and otolaryngology is pursuing.
"Many hearing losses are genetically programmed to show up later in life," says Burkard. "There is quite a bit of evidence to indicate that age-related hearing loss may be a result of a genetic inability to clean up free radicals. If we know that the gene turns on at, say, 60, we can be poised to do something about it. Once we have ideas concerning the causes, we are in a better position to approach a treatment or cure."
The mysterious, pliable brain
The research of several center researchers in the field of brain plasticity has more immediate clinical applications. It is known that the neuronal network responsible for hearing reorganizes itself after damage to inner hair cells; it changes the channel to get better reception, in a sense.
Sandra McFadden, research assistant professor at the center, and Henderson have found that a poorly understood segment of the auditory organs called the efferent system may play a role in permanent hearing loss.
Anatomically, the efferent system is a large bundle of fibers running from the brain to the cochlea that functions as a feedback mechanism. "We're one of the first laboratories to show that if you cut the efferent fibers in one ear, those ears show more damage from noise," McFadden says. "It appears the efferent system may be important for hearing during noisy situations."
McFadden also is investigating the potential role of estrogen as a protectant against hearing loss. Hers is the first study to look at the hormone in this context. Working with chinchillas, she found that noise exposure caused less damage in animals receiving estrogen than in those that didn't. These results suggest that estrogen, like gluthathione peroxidase, may act as an antioxidant.
Knowledge is power in nearly every endeavor, and this is particularly true in basic scientific research. Understanding how hearing is lost and how it can be recovered or its loss prevented will make possible the development of new devices and therapies that will brighten the lives of millions of people.
The future for understanding and treating hearing loss and other hearing disabilities looks bright, Salvi says. "Drawing from brain imaging, genetics, neuroscience, molecular biology, and biochemistry, we now have a whole arsenal of weapons at our disposal, allowing us to look at acquired hearing loss at the molecular level," he says, "to those that let us look at the whole brain at once."