The current research study is being reported in the upcoming issue of Proceeding of the National Academy of Sciences and will also be published online as well. The researchers focused on the suppression of retinoblastoma (Rb) protein. They discovered that changing the protein had different effects in the inner ear.
"In these first studies of the role of the Rb protein in the ears of postnatal mice, we have confirmed that - under the right conditions - mature hair cells can go through the cell cycle and produce new, functioning hair cells. But we've also confirmed that you need to block Rb reversibly and at an early stage of development, otherwise the hair cells will die," said Zheng-Yi Chen, DPhil, of the MGH Neurology Service who is the study's senior author.
The hair cells are very sensitive and can be damaged by loud noise, infections and toxins. If damage occurs to the hair cells they die and cause hearing loss of the inner ear.
In their first study they used the Rb protein was blocked from being made in mice to simulate hearing impairment. These genetically altered mice treated with Rb protein had more hair cells compared to the normal mice at the same embryonic developmental stage. The modified mice did not survive past birth. They hair cells looked normal and they looked like they were actively regenerating.
The current study the researchers developed a new strain of inner ear Rb knockout mice which some survived up to 6 months after birth. The Rb-negative auditory hair cells in the born mice showed hair cells that were dividing and growing. They found that the hair cells did not develop properly and they eventually died with the mice becoming deaf around 3 months after being born.
The researchers found that vestibular hair cells grew and matured in a normal manor even as the Rb-knockout mice aged. In the adult Rb-knockout mice some mice had vestibular function that allowed for them to have a sense of balance.
"We've shown that vestibular hair cell regeneration may be achieved and may be less of an obstacle than auditory cell regeneration," Chen says. "Now we need to find ways to create a similar system in the auditory cells, and this new model will help us better understand the mechanisms behind functional hair cell regeneration. Our next step will be developing a transient, reversible block of Rb function to assess its role in both types of hair cell." Chen is an assistant professor of Neurology of Harvard Medical School.