New research marks an important step toward what may become a new approach to restore hearing loss.
Scientists have been able to regrow the sensory hair cells found in the cochlea—a part of the inner ear—that converts sound vibrations into electrical signals and can be permanently lost due to age or noise damage.
An estimated 30 million Americans suffer from some degree of hearing loss—and people have long been accepted it as a fact of life for the aging population. But animals, including birds, frogs, and fish, can regenerate lost sensory hair cells.
“It’s funny, but mammals are the oddballs in the animal kingdom when it comes to cochlear regeneration,” says study coauthor Jingyuan Zhang of the biology department at the University of Rochester. “We’re the only vertebrates that can’t do it.”
Pathway switch
In 2012, researchers identified a family of receptors called epidermal growth factor (EGF) that are responsible for activating support cells in the auditory organs of birds. When triggered, these cells proliferate and foster the generation of new sensory hair cells. Scientists speculated that they could potentially manipulate this signaling pathway to produce a similar result in mammals.
“In mice, the cochlea expresses EGF receptors throughout the animal’s life, but they apparently never drive regeneration of hair cells,” says lead author Patricia White, research associate professor in the University of Rochester Medical Center (URMC) Del Monte Institute for Neuroscience.
“Perhaps during mammalian evolution, there have been changes in the expression of intracellular regulators of EGF receptor family signaling. Those regulators could have altered the outcome of signaling, blocking regeneration,” White says.
“Our research is focused on finding a way switch the pathway temporarily, in order to promote both regeneration of hair cells and their integration with nerve cells, both of which are critical for hearing,” she explains.
“This research… could represent a new approach to cochlear regeneration and, ultimately, restoration of hearing.”
In the new study, the team tested the theory that signaling from the EGF family of receptors could play a role in cochlear regeneration in mammals. The researchers focused on a specific receptor called ERBB2 in cochlear support cells.
They investigated a number of different methods to activate the EGF signaling pathway. One set of experiments involved using a virus to target ERBB2 receptors. Another, involved mice genetically modified to overexpress an activated ERBB2. A third experiment involved testing two drugs, originally developed to stimulate stem cell activity in the eyes and pancreas, that are known activate ERBB2 signaling.
Complex problem
The researchers found that activating the ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to proliferate and start the process of activating other neighboring stem cells to become new sensory hair cells.
Further, it appears that this process not only could affect the regeneration of sensory hair cells, but also support their integration with nerve cells.
“The process of repairing hearing is a complex problem and requires a series of cellular events,” White says. “You have to regenerate sensory hair cells and these cells have to function properly and connect with the necessary network of neurons.
“This research demonstrates a signaling pathway that can be activated by different methods and could represent a new approach to cochlear regeneration and, ultimately, restoration of hearing,” she says.
The research appears in the European Journal of Neuroscience.
Additional researchers are from URMC and the Massachusetts Ear and Eye Infirmary, which is part of Harvard Medical School. The National Institute for Deafness and Communication Disorders supported the work.
Source: University of Rochester
