The researchers found that a protein called NT3 is important for establishing ribbon synapses (red) - connections between the inner ear's hair cells (blue) and nerve cells (green).
Image credit: Corfas laboratory - University of Michigan
The researchers, led by Gabriel Corfas, PhD, of the University of Michigan, publish their findings online in the journal eLife.
Approximately 50 million Americans have hearing loss in at least one ear, with around 26 million Americans aged 20-69 experiencing high-frequency hearing loss as a result of noise exposure. Hearing loss is also common as we age, affecting around 30% of adults aged 65-74 and 47% of adults aged 75 and over.
In their study, the researchers explain how they were able to increase production of a protein called Neurotrophin-3 (NT3) in mice, which they found plays a key role in communication between the ears and the brain.
NT3 allows sound signals to be sent from the ear to the brain. The protein is crucial in establishing a super-fast connection between the ear's hair cells and nerve cells - a connection the researchers call the "ribbon synapse." But this ribbon synapse can become damaged as a result of noise exposure or normal aging, which can lead to hearing loss.
Boosting NT3 production in mice
In their study, the researchers identified supporting cells in the inner ear that produce NT3. They set out to see what would happen if they increased production of NT3 through these supporting cells.
- Hearing loss is more common among men than women
- Around 60% of veterans returning from Iraq or Afghanistan have some form of hearing loss or tinnitus - ringing in the ears
- Approximately 2-3 in every 1,000 children in the US are born with detectable levels of hearing loss in one or both ears.
They adopted a method called conditional gene recombination. This allows researchers to activate genes in particular cells by administering a drug that prompts the cells to "read" additional copies of a gene that have been inserted into them.
For this study, the team used the technique to activate additional NT3 genes that had been introduced to the supporting cells of the inner ear in mice that had been partially deafened by loud noise.
The drug tamoxifen was introduced to the supporting cells in the inner ear, which prompted them to produce extra NT3 protein. The researchers then tested the hearing of the mice through a test normally used in humans - the auditory brainstem response (ABR).
The researchers found the mice that had experienced boosted NT3 production regained their hearing over a 2-week period, compared with mice that had not had additional NT3 production.
According to the team, these findings indicate that NT3 production is important for making ribbon synapses, and that boosting production of this protein may restore noise-induced and age-related hearing loss.
The potential to restore hearing loss in humans
Corfas and his team say they now plan to investigate the role of NT3 in human ears and identify drugs that produce the same effect as the protein, offering the potential to restore hearing loss in humans.
The researchers note that the gene therapy technique used in this study has the potential to work in humans, but that a drug-based method would be "simpler" and a drug could be repeatedly administered for as long as it takes for hearing to be restored. Corfas says he already has some drug candidates in mind.
The researchers stress, however, that since the mice in this study were only partially deaf, it is unclear whether increased NT3 production would restore hearing in subjects that are fully deaf.
But the team believes their findings are promising. Corfas says:
"It has become apparent that hearing loss due to damaged ribbon synapses is a very common and challenging problem, whether it's due to noise or normal aging. We began this work 15 years ago to answer very basic questions about the inner ear, and now we have been able to restore hearing after partial deafening with noise, a common problem for people. It's very exciting."
Their findings may even reach further than hearing loss. The researchers say they may offer new strategies to treat neurodegenerative diseases, in which nerve cell connections are impaired.
Medical News Today recently reported on a study from the University of Leicester in the UK, in which researchers reveal how loud noises damage hearing in more detail.