Hearing Loss

Epidemiology and Treatment of Hearing Loss

Hearing loss is one of the most pervasive diseases in the U.S., affecting Americans from the time they are born (0.2% fail newborn screening), increasing through adolescents (evidence of hearing loss in 10% of Americans at age 12 and older) and becoming the norm in the elderly (disabling levels of hearing loss in 50% of Americans 75 and older). These rates are growing as toxic levels of environmental exposure in developed countries (e.g., urban living, ear buds, industrial work place) becomes more prevelant.

Treatment of HL has been mostly restricted to amplification devices (i.e., hearing aids) or through cochlear implants. While both hearing aids and cochlear implants have been incredibly successful in maintaining some level of continued hearing functionality, they do little to prevent additional progression of the disease. Recent advances in the understanding of the genetics and pathology of auditory dysfunction have started to suggest molecular therapies that may stop or even reverse the progression of HL.

Anatomy of the Ear

We hear through the detection of pressure waves created in the atmosphere. These pressure waves are collected by the outer ear, transmitted through the middle ear and then are processed in the inner ear. The inner ear is contained within a shell like bony structure known as the cochlea. Inside the cochlea pressure waves cause movement of the organ of Corti. This movement causes channels at the top of cells known as hair cells to open and close. Opening of these channels cause the cell to depolarize, resulting in an action potential that sends a signal to the brain.

Problems associated with the outer and middle ear (e.g., deformaties, rupture of the ear drum, "water in the ear") cause what is known as conductive hearing loss and are typically correctable through removing blockages or surgery. Problems associated with the inner ear are known as sensorineural hearing loss and are often progressive and more difficult to correct. Rare conditions cause degeneration of the nerves to or from the inner ear resulting in auditory neuropathy and have very few medical interventions.

Physiology and the Cochlear Amplifier

The organ of Corti is a beautiful example of evolution's ability to create complex bioengineering. It is still not completely clear how the inner ear processes the complex auditory stimulus, but it has been shown that the inner ear has the ability to amplify the auditory signal. This cochlear amplification process is thought to be performed by certain hair cells in the inner ear known as outer hair cells (OHC). OHCs have a unique property that they can change their shape when depolarized in a process known as somatic motility (SM). It is thought that this SM can place energy back into the auditory system and cause cochlear amplification. In 2000, it was discovered that SM is due in part to the role of a protein unique to mammalian inner ear known as prestin.

During my graduate work, I focused my research on SM and specifically prestin's role in cochlear amplification. Perhaps one of the most revealing studies examined the structure-function relationship of prestin showing that it likely formed a tetramer that shared similar structure to known transmembrane channels.

Genetics of Hearing

There is a strong genetic component to hearing loss with 50% of both congenital and age-related hearing loss attributed to a genetic component. To date, hearing loss geneticists have been very successful and there are now over 100 genes and genetic loci associated with Mendellian forms of hearing loss. In more recent years, there has been an acceleration of gene discovery in hearing loss with the advancement of next-generation sequencing technologies. However, the genetic cause of most hearing loss cases remains undiagnosed, leaving a gap in possible therapeutic interventions.

During my postdoctoral research, I have been involved in the discovery of genetic forms of hearing loss. Through the Developmental Genome Anatomy Project (DGAP), we have identified or confirmed several genetic causes of congenital hearing loss. More recently, we have been working on collaborations to perform genome-wide association studies (GWAS) of the genetic causes of age-related hearing loss. This work promises to discover many new genes and accelerate diagnostic methods involved in hearing loss. Once the underlying genetic etiology is known, precision medicines can be developed or applied to preventing hearing loss.