Molecular biology of hearing loss

The molecular processes involved in the production of neurotrophins in the auditory system

Sensorineural hearing loss is caused by damage to sensory hair cells in the inner ear. These hair cells can be damaged by traumatic noise, excessive exposure to ototoxic antibiotics and exposure to certain anti-cancer drugs such as cis-platin.

Work from our laboratory and others have shown that these sensory hair cells are a source of neurotrophins – small protein molecules that promote survival of the primary auditory neurons that connect with these cells. These neurotrophins are secreted and captured by neurotrophin receptors expressed on the surface of primary auditory neurons.

Recently, we have shown that one particular neurotrophin receptor, the p75 neurotrophin receptor, is strongly up-regulated in primary auditory neurons and another class of cells in the inner ear – the Schwann cells. The reason for this increased expression is unclear and we are working towards clarifying the role of p75 neurotrophin receptor during episodes of inner ear trauma. Because p75 neurotrophin receptor is so dramatically increased, it is a potential candidate for targeting therapeutic drugs into the inner ear.

Can prenatal supplementation of thyroid hormone prevent hearing loss?

Mutations in transmembrane serine proteases cause the deafness syndrome in humans - DNFB8/10.

Cochlear pathologies in these affected humans are unknown. The use of a mouse model can provide clues to how these genes affect the development and function of the cochlea. Analysis of mutant mice lacking the transmembrane serine protease gene, tmprss1, shows deficient hearing responses and abnormalities in the anatomy of the cochlea. These mice are also hypothyroid. Because thyroid hormones are important for development of the cochlea and brain, we performed thyroid hormone supplementation during embryonic development.

If prenatal thyroid hormone supplementation is proven successful, this therapy can help clinicians formulate an approach to rescue hearing in newborns of parents affected by such gene mutations.

Funding

The Garnett Passe and Rodney Williams Memorial Foundation and US National Institutes of Health(HHS-N-263-2007-00053-C)