Microscope image of tissue from deep inside a normal mouse ear
This microscope image of tissue from deep inside a normal mouse ear shows how ribbon synapses (red) form the connections between the hair cells of the inner ear (blue) and the tips of nerve cells (green) that connect to the brain. Corfas Lab, University of Michigan

Scientists from the University of Michigan Medical School, Harvard University and the Massachusetts Eye and Ear Infirmary have succeeded in restoring hearing in noise-deafened mice by activating a protein to repair crucial connections in the inner ear, which could one day be used to treat patients with hearing loss.

Neurotrophin-3 (NT3) is a protein that supports the survival of neurons in the central nervous system and also encourages the growth of new neurons and synapses in the body.

Until now, cells that produce NT3 have traditionally been seen by scientists to be "supporting actors" in the ear-brain nerve connection, forming a physical base for the hair cells that interact directly with nerves to carry sound signals to the brain from the ear.

The scientists' research has shown that not only is NT3 crucial to the body's ability to form and maintain connections between hair cells and nerve cells, but it is also possible to stimulate the production of NT3 by stimulating genes in inner ear cells.

Their study, entitled "Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma" has been published in the journal eLife.

The scientists realised NT3 helped to form and maintain ribbon synapses, a special type of connection that enables the super-fast communication of electrical impulses from hair cells to nerve cells, once mechanical sound waves have been converted into impulses by a protein called TMHS.

When a person experiences a temporary reduction in hearing after going to a concert, for example, this is caused by noise damage reducing the ribbon synapses in the inner ear.

Over a long period of time, repeated noise can drastically reduce the ability of hair cells to convey impulses to the brain via ribbon synapse connections.

After discovering inner ear cells in mice supplied NT3, the scientists inserted extra copies of NT3 genes into certain cells and then gave the mice a dose of tamoxifen, a drug that caused specific cells in the inner ear to activate the newly-inserted NT3 genes.

Once the genes were activated, the cells produced more of the NT3 protein, which repaired ribbon synapses.

The mice that produced extra NT3 regained their hearing over a period of two weeks and were able to hear a lot better than mice that did not have extra production of the protein.

"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," said Dr Gabriel Corfas, who led the team and directs the University of Michigan Medical School's Kresge Hearing Research Institute.

"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."

Corfas says that the next step will be to test how NT3 works in human ears, but instead of inserting genes into humans, the scientists plan to look for drugs that can perform the same function that NT3 does to repair ribbon synapse connections.