New mechanism of inner-ear repair discovered

New mechanism of inner-ear repair discovered

A new mechanism of inner-ear repair has been discovered by researchers at the University of Kentucky.

The team developed a two-step mechanism which allows molecular structures within the ear to rebuild themselves after being damaged by exposure to extremely loud noises - which can cause hearing loss.

The World Health Organization currently estimates that there are over 360 million people in the world living with disabling hearing loss.

The latest findings were published in the journal PLOS Biology.

A main cause of hearing loss is when the 'tip links' in the inner ear begin to break. These delicate protein chains are located in the hair cells of the inner ear, they take several hours to re-form and restore mechanosensitivity.

A process known as "mechanotransduction" helps the brain detect sound waves. Sound vibrations make the hairs (stereocilia) in the ear move back and forth, which results in the emission of electrical impulses that the brain interprets as sound.

Tip links connect the tips of stereocilia in adjacent rows in the bundles and open up ion channels which promote mechanotransduction.

They are composed of two different proteins:

  • protocadherin-15 (PCDH15) - Located closest to the shorter stereocilium
  • cadherin-23 (CDH23) - Links to the longer stereocilium
When these proteins mutate it can result in deafness.

The team, led by Gregory I. Frolenkov, an associate professor of physiology at the University of Kentucky College of Medicine, discovered that PCDH15 triggers the re-formation of the chain and as soon as CDH23 is back in place there is full restoration of normal mechanotransduction.

Mouse hair cells were treated with a calcium-free solution which blocked all the links connecting the stereocilia, which prevented normal mechanotransduction. Using scanning electron microscopy the investigators observed tip link regeneration.

New links were formed at the top of the stereocilium within the first few hours, and over the next day Mechanosensitivity slowly returned to normal. However, fast adaptation, a property of normal mechanotransduction response, remained abnormal for the following 36 hours before recovering.

Changes in the molecular composition of the restored tip links were linked to the final normalization.

The Role of Hair Cells in Hearing

The two step process

Following the disruption of stereocilia, PCDH15 was instantly redistributed along its surface while CDH23 mainly disappeared.

The amount of PCDH15 increased as the links began to re-form, whereas the amount of CDH23 was still low, in comparison to those in the control group who who received treatment.

PCDH15 was found at both ends of the links in the mice who were treated with the calcium as opposed to just in the lower end in the controls, which indicates that PCDH15 was trying to replace CDH23 as the links re-formed.

When the links were completely in place, CDH23 slowly restored along with the recovery of normal mechanotransduction.

The inner ear interprets sound via tip links that open up ion channels.

Image credit: Gregory I. Frolenkov.

This two-step process also occurred when mouse's hair cells initially developed.

Dr. Frolenkov, concluded:

"This study resolves a dispute over the composition of tip links, in which one camp argued for a PCDH15-only structure, and the other for a combination of the two proteins. Apparently, both are right, depending on when one looks. More importantly, it reveals the details of a process that is likely to be vital for the development, maintenance, and restoration of normal hearing."

Short-term hearing loss is the body's way of coping

Another study published in the prestigious journal Proceedings of the National Academy of Science (PNAS), revealed that short-term hearing loss following sustained exposure to loud noise doesn't reflect damage to our hearing: rather, it is the body's way of coping.

Short-term hearing loss occurs when sound levels rise and the cells in the cochlea release a hormone called ATP, which binds to a receptor resulting in temporary reduction in hearing sensitivity.

Stem Cell Treatment For Hearing Loss (Video Medical And Professional 2020).

Section Issues On Medicine: Disease