Successful production of functional sensory hair cells in the inner ears of mice suggests that a new therapy to regain hearing may be possible
August 27, 2008 - Portland, Ore.- Oregon Health & Science University scientists have successfully produced functional auditory hair cells in the cochlea of the mouse inner ear. The breakthrough suggests that a new therapy may be developed in the future to successfully treat hearing loss. The results of this research will be published online this week by the journal Nature.
"One approach to restore auditory function is to replace defective cells with healthy new cells," said John Brigande, Ph.D., an assistant professor of otolaryngology at the Oregon Hearing Research Center in the OHSU School of Medicine. "Our work shows that it is possible to produce functional auditory hair cells in the mammalian cochlea."
The researchers specifically focused on the tiny hair cells located in a portion of the ear's cochlea called the organ of Corti. It has long been understood that as these hair cells die, hearing loss occurs. Throughout a person's life, a certain number of these cells malfunction or die naturally leading to gradual hearing loss often witnessed in aging persons. Those who are exposed to loud noises for a prolonged period or suffer from certain diseases lose more sensory hair cells than average and therefore suffer from more pronounced hearing loss.
Brigande and his colleagues were able to produce hair cells by transferring a key gene, called Atoh1, into the developing inner ears of mice. The gene was inserted along with green florescent protein (GFP) which is the molecule that makes a species of jellyfish glow. GFP is often used in research as a "marker" that a scientist can use to determine, in this case, the exact location of the Atoh1 expression. Remarkably, the gene transfer technique resulted in Atoh1 expression in the organ of Corti, where the sensory hair cells form.
Using this method, the researchers were able to trace how the inserted genetic material successfully led to hair cell production resulting in the appearance of more hair cells than are typically located in the ears of early postnatal mice. Crucially, Dr. Anthony Ricci, associate professor of otolaryngology at the Stanford University School of Medicine, demonstrated that the hair cells have electrophysiological properties consistent with wild type or endogenous hair cells, meaning that the hair cells appear to be functional. Based on these data, the scientists concluded that Atoh1 expression generates functional auditory hair cells in the inner ear of newborn mammals.
"It remains to be determined whether gene transfer into a deaf mouse will lead to the production of healthy cells that enable hearing. However, we have made an important step toward defining an approach that may lead to therapeutic intervention for hearing loss," Brigande said.
About the Oregon Hearing Research Center at OHSU
The Oregon Hearing Research Center at the Oregon Health & Science University is comprised of over 50 scientists and support staff engaged in basic and applied research into the causes and treatment of hearing disorders. Established in 1966 by Jack Vernon, Ph.D., the Center is currently under the direction of Alfred Nuttall, Ph.D. Sources of research support come from the National Institutes of Health and private hearing research organizations.
About OHSU
Oregon Health & Science University is the state's only health and research university, and Oregon's only academic health center. OHSU is Portland's largest employer and the fourth largest in Oregon (excluding government), with 12,400 employees. OHSU's size contributes to its ability to provide many services and community support activities not found anywhere else in the state. It serves patients from every corner of the state, and is a conduit for learning for more than 3,400 students and trainees. OHSU is the source of more than 200 community outreach programs that bring health and education services to every county in the state.
As a leader in research, OHSU earned $307 million in research funding in fiscal year 2007. OHSU serves as a catalyst for the region's bioscience industry and is an incubator of discovery, averaging one new breakthrough or innovation every three days, with more than 4,100 research projects currently under way. OHSU disclosed 132 inventions in 2007 alone, and OHSU research resulted in 33 new spinoff companies since 2000, most of which are based in Oregon.
