Genetic mechanism implicated in age-related hearing loss discovered

A gene has been identified in mice that allows the differentiation of inner cochlear hair cells in the ear from outer cochlear hair cells.

The death of outer cochlear hair cells is responsible for some forms of old age hearing loss in humans, as these cells do not renew after birth. When sound enters the ear, the outer hair cells expand and contract in response to the pressure of sound waves and amplify the sound for the inner hair cells. The inner hair cells then transmit those vibrations to nerve cells, which in turn allow us to make sense of the sound in our brain.

Professor Jaime García-Añoveros, professor of anesthesiology and neuroscience at Northwestern University in Chicago, Illinois and study author said: 'It's like a ballet. The outers crouch and jump and lift the inners further into the ear. The ear is a beautiful organ. There is no other organ in a mammal where the cells are so precisely positioned. I mean, with micrometric precision. Otherwise, hearing doesn't occur.'

While scientists were previously able to grow new cochlear hair cells in the lab, they were unable to further differentiate them into either inner or outer hair cells. This had posed a challenge for developing treatments for old age hearing loss.

Researchers at Northwestern University have now discovered that when a gene called TBX2 is expressed in cochlear hair cells, they develop into inner hair cells, whereas when TBX2 is blocked, the cells become outer hair cells. Professor García-Añoveros said: 'Our finding gives us the first clear cell switch to make one type versus the other. It will provide a previously unavailable tool to make an inner or outer hair cell. We have overcome a major hurdle'.

The research, published in Nature, showed that it was possible to produce inner and outer hair cells from cochlear cells in mice. Two genes, ATOH1 and GF1, are first needed to create cochlear hair cells from non-hair cells and TBX2 will then either be switched on or off to push the cells to develop into inner hair cells or outer hair cells respectively.

Professor García-Añoveros said: 'We need to also generate the right type of supporting cells. We are making progress in figuring this out. The other [challenge] is that the newly generated inner or outer cells will need to be reconnected with the brain by the right neurons – nerves connecting the cochlea and the brain. We are also advancing on this front. The ability we now have to switch a cell from an inner hair cell to an outer hair cell and vice versa permits us to explore these matters, which were close to intractable before. Our research overcame only one major hurdle [and] it is paving the way for overcoming the next ones.'