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      New research – switching on hair cell regeneration

      Researchers in the US have uncovered the role of a protein called ERBB2 in the processes underlying hair cell regeneration. Their findings could one day lead to a new approach to restoring hearing in people. Tracey Pollard, from our Biomedical Research team, tells us more.

      By: Dr Tracey Pollard | 16 November 2018

      Hearing loss is estimated to affect over 11 million people in the UK alone – most of this is due to ageing or exposure to loud noise, which damages the sound-sensing hair cells in the inner ear. Hearing loss in people is permanent – once hair cells are damaged and die, they don’t re-grow. But other types of animal – such as birds, reptiles and amphibians – can re-grow their lost hair cells, so to them, hearing loss is temporary. It seems that only mammals (like us) can’t re-grow hair cells – and no-one really understands why.

      So to re-grow hair cells in people, and restore their hearing, we need to find a way to ‘switch on’ the processes that lead to hair cell re-growth, or ‘regeneration’, in other animals. Researchers all over the world have been trying to find out what these processes are, why they’re switched off in mammals, and how to switch them on again.

      EGFR proteins – could they be involved?

      Recently, researchers have been focusing on how a specific group, or ‘family’, of proteins, called the EGFR family, might be involved in regenerating hair cells. This protein family are active in many other organs of the body, such as the muscles or the lungs, where they are activated by damage caused by tissue stretching – and they cause cells in the damaged organ to replicate and repair it. It’s possible that these proteins could do something similar in the inner ear (cochlea) in response to damage caused by exposure to loud noise.

      The EGFR protein family are known to be involved in repairing damaged hearing in birds – they stimulate supporting cells in the cochlea to replicate. Supporting cells, as their name suggests, support hair cells by providing them with a physical framework to grow around. They also maintain them in perfect health, allowing them to carry out their roles of detecting sound and transferring the information to the brain. In animals that are able to re-grow hair cells (like birds), it’s the supporting cells that are the source of these new cells – they replicate themselves and the resulting cells turn into hair cells, to replace the cells that are lost.

      In addition, one particular member of the EGFR family, called ERBB2, has previously been shown to promote the replication of supporting cells in the vestibular (balance) system of the inner ear (which are similar to those found in the cochlea).

      So there is definitely some evidence to suggest that EGFR proteins have a role in hair cell regeneration, but it’s still not clear what that role is, or how the proteins carry out that role.

      Deiters
      Supporting cells: (image provided by Professor David Furness, Keele University) This image shows supporting cells (called Deiters’ cells) and outer hair cells. Each outer hair cell (identified by the ‘hairs’ seen at the top of the image, with the main body of the hair cell then extending downwards towards the back of the image) ‘sit’ on the main body of one Deiters’ cell (seen at the bottom of the image, towards the front). Each Deiters’ cells extends a thin process upwards towards the top of the image, which provides further physical support to the hair cells. Image kindly provided to us by Professor David Furness, at Keele University.

      Looking at ERBB2 in more detail

      To get hair cell regeneration to work successfully, at least two things need to happen: supporting cells have to replicate themselves, and then those new cells need to turn into hair cells.

      A team of researchers at the University of Rochester in the USA, led by Dr Patricia White, alongside collaborators at Harvard University, have been studying ERBB2 and its possible role in hair cell regeneration. They’ve been using a variety of different research methods to help them figure out what it does, where in the cochlea it does it, and how.

      The team have done this by studying cochlear cells (including hair cells and supporting cells) in a dish in the lab, in structures called explants, and also in the inner ears of mice directly. They have used different ways to control the activity of ERBB2 in supporting cells in these two systems. In explants, they switched ERBB2 activity on permanently in supporting cells, and looked at the effect this had on hair cell regeneration processes. They found that more supporting cells replicated themselves when ERBB2 was permanently activated – suggesting that ERBB2 can induce supporting cells to replicate, one of the processes needed for correct hair cell regeneration.

      When they switched ERBB2 activity on permanently in the inner ears of mice, they found an increased number of hair cell-like cells in the cochlea, which were producing a number of the proteins that we know are needed for a hair cell to be a hair cell. This suggests that ERBB2 can induce supporting cells to turn into these hair cell-like cells, another part of the process needed for hair cell regeneration.

      Finally, they went back to explants of cochlear cells in which ERBB2 activity was normal, and used small molecules (like drugs) to activate ERBB2 in these cells. They saw both supporting cell replication and an increase in the number of hair cell-like cells in the explants.

      Supporting cells cochlea - ‘Supporting cells in the cochlea (image provided by Professor Ed Rubel, University of Washington
      Supporting cells in the cochlea: (image provided by Professor Ed Rubel, University of Washington. This image shows a sideways-on view of the mouse inner ear (cochlea), showing hair cells in faint blue. Supporting cells are identified by the thick and thin green bundles in front of the hair cells, which form the ‘skeleton’ that supports the hair cells. Nerve cells connecting to the hair cells can be seen as thin red lines behind the green bundles of the supporting cells. Image kindly provided to us by Professor Ed Rubel, at the University of Washington.

      So what does this mean?

      From the team’s findings, it appears that the EGFR protein family, especially ERBB2, may be crucial for hair cell regeneration. Drugs that target this protein could therefore promote the regeneration of hair cells and help to restore hearing due to hair cell damage.

      Find out more

      The research described in this blog was published last month in the journal European Journal of Neuroscience – you can read the abstract here.

      We depend on your donations so we can fund the best hearing and tinnitus research around the world. Donate today and help us continue our vital work into hearing treatments, so that people can live life to the full again.

      You can find out more about the research we’re funding in our biomedical research section.

      If you’re interested in finding out more about our research, sign up to receive our Soundbite newsletter. It’s a monthly email, filled with the latest news about hearing and tinnitus research.

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