A new research study has now yielded valuable clues about regeneration of hearing cells present in the ear, which convert sound vibrations into nerve impulses, to be processed by the brain. //
Researchers at the Massachusetts General Hospital (MGH) have developed a mouse model that would allow further research regarding deactivation of a retinoblastoma protein (can be achieved through knock out of retinoblastoma gene) that is thought to play a major role in the growth and division of hair cells. Suppression of this protein has already been known to result in variable effects in specific parts of the inner ear. The results of this study that holds a promise in the research and treatment of hearing loss would be presented in the upcoming issue of Proceeding of the National Academy of Sciences.
‘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,’ says Zheng-Yi Chen, DPhil, of the MGH Neurology Service, the study's senior author. In 2005 Chen was named to the Scientific American 50, the magazine's annual list of outstanding leaders, for this continuing research project.
Named for the hair-like projections on their surfaces, hair cells form a ribbon of vibration sensors along the length of the cochlea – the organ of the inner ear that senses sound – where they convert sonic vibrations to electrical signals that are carried to the brain. The cells are very sensitive to damage from excessive noise, infections and toxins. Once damaged, hair cells do not naturally regenerate in mammals, and their death accounts for most types of acquired hearing loss.
All cells grow and divide through a process called the cell cycle, and ma
ny proteins have been identified that control different cell cycle phases. In 2005 Chen's group published a paper in the journal Science reporting that the Rb protein, known to suppress the cell cycle, could be important for halting the cell cycle in hair cells. They used a genetically modified mouse strain in which Rb was no longer made in the inner ear. By examining the inner ears of mouse embryos – that strain did not survive past birth – the researchers found more hair cells in the knockout mice than in the ears of normal mice at the same stage of development. The additional cells looked and functioned like normal hair cells and appeared to be actively regenerating.
For this follow-up study, the researchers developed a new strain of inner-ear Rb-knockout mice that survive for up to six months past birth. Their investigation of the effects of Rb deletion on the hair cells of the inner ear finds differences between the auditory portion of the organ, which controls hearing, and the vestibular area, which is involved with balance. While the Rb-negative auditory hair cells in early postnatal mice are dividing and growing, the cells do not mature properly and eventually die, resulting in the mice becoming deaf by the age of 3 months. Vestibular hair cells, however, appear to grow and mature relatively normally and continue cell division even in mature mice. Adult Rb-knockout mice maintain some vestibular function, indicating that those hair cells are contributing to their sense of balance at the system level.
'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 ha
ir cell.' Chen is an assistant professor of Neurology of Harvard Medical School (HMS).
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