Hear, hear
Corwin’s research aims to reverse hearing loss

By Fariss Samarrai

Take a chicken to a loud rock concert and chances are the chicken will understand the lyrics about as well as you will. But about 10 days later, while you are suffering from irreparable hearing loss, the chicken will begin to recover its hearing.

Is this weird? Sure. Most non-mammals — birds, amphibians, fish — can regenerate the hearing and balance cells of the inner ear throughout their lives. But mammals, including humans, stop growing these cells while still in the womb, and will never again grow new ones.

Unless Jeff Corwin has anything to say about it.

Corwin, a U.Va. professor of otolaryngology and neuroscience, is looking for ways to replace damaged hearing and balance cells of the inner ear. All of his work is conducted in the lab on the sensory cells of mouse, rat, and chicken specimens, but the work should translate to humans.

“We hope that eventually our research will improve the quality of life for people who suffer from hearing loss and the balance disorders that currently are considered irreversible,” he said. “The work may lead to the development of effective treatments.”

More than 20 million Americans have persistent hearing loss, the result of the loss of sensory cells. Many older people have balance problems that also can result from losing balance cells in the ear.

Corwin began his career at Cornell University as a biologist. He later focused his studies on the inner ear detectors of sharks, skates and rays at the University of Hawaii and the University of California-San Diego, where he earned a Ph. D. in neurosciences.

He was fascinated to discover that sharks’ inner ears, which were once considered primitive, actually had far more sensory cells than the human inner ear because they were able to add new hearing and balance cells throughout life. A juvenile shark has about 20,000 cells, while an adult eventually generates 240,000. Human ears have about 16,000 hearing cells at birth, and the number declines with age.

“I became interested in trying to figure out whether regenerative replacement could lead to recovery from cell loss,” Corwin said. “I wrote a proposal to NIH to look for regeneration and for ways to eventually stimulate replacement of damaged hearing and balance cells in mammals.”

Corwin got the NIH funding, which has continued for 21 years. He and his colleagues are getting closer to finding ways to stimulate the regeneration of neurosensory cells and to preventing their loss.

The hearing and balance cells of the inner ear are microscopic and hair-like in structure. These sensory cells pick up the vibrations of sound, and encode them as signals for the brain. Balance hair cells also help us maintain balance by allowing our nervous systems to rapidly and automatically reposition our eyes to compensate for the motion of our head and stabilize our visual world as we move.

Corwin said we lose these cells throughout our lives as a normal part of aging. We also can lose cells when exposed to loud noises, infections and some medicines, such as certain antibiotics.

“Hearing loss and balance problems increase as people age,” he said.
Half of all people over 70 have significant hearing loss and many elderly people injure themselves from falls that may be related to balance problems and loss of inner ear cells.

“There are profound psychological effects from loss of hearing,” he said. “It can affect a person’s ability to interact socially, although for people who are deaf from birth, the situation is quite different.”

Corwin and his team conduct their research on cells in tissue culture.

Together with colleagues at U.Va. and elsewhere they are using stem cells to look for ways to specifically grow hearing and balance cells.
“We’ve been able to stimulate growth of mammalian ear cells in culture,” Corwin said. “But we need to understand a spectrum of molecular signals so we can control cell replacement in the ear.”

Jason Meyers, Themis Karaoli, Dawn Davies, Mark Ranck and Victoria Chiou in Corwin’s group are determining what causes hearing and balance cells to stop growing in mammals. Understanding what causes the halt is important to learning how to restart the process and stimulate healing where there is damage.

Because stem cells have to specialize to become hearing and balance cells, Corwin’s work draws on results from cancer research and developmental biology. By understanding the molecular signals that turn on or off the development of particular cells, scientists could apply that knowledge to better understanding how normal and cancerous cells proliferate.

Catharine Cowan, Jason Meyers, and Stefanie McCormack in Corwin’s team use time-lapse micro-imaging of cell replacement and growth, capturing images of the cells in culture every few minutes for days. Then they can “turn the direction of time backwards” by running the images in reverse for an action narrative that visually tells how the replacement cells arose.

“If we could someday regenerate cells in the human ear, we could see dramatic improvements for people with hearing damage,” Corwin said. “This area of research may be one of the first places where regenerative medicine could work.”