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 was recently published 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.
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