A small striped fish is helping scientists understand what makes people susceptible to a common form of hearing loss, although, in this case, it's not the fish's ears that are of interest.
In a study published on February 29 in the open-access journal PLoS Genetics, researchers at the University of Washington have developed a research method that relies on a zebrafish's lateral line—the faint line running down each side of a fish that enables it to sense its surroundings—to quickly screen for genes and chemical compounds that protect against hearing loss from some medications. The study was funded in part by the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health.
“The fish's lateral line contains sensory cells that are functionally similar to those found in the inner ear, except these are on the surface of the fish's body, making them more easily accessible,” said James F. Battey, Jr., M.D., Ph.D., director of the NIDCD. “This means that scientists can very efficiently analyze the sensory structures under different conditions to find out what is likely to cause damage to these structures and, conversely, what can protect them from damage.”
When people are exposed to some antibiotics and chemotherapy agents, the sensory structures in the inner ear, called hair cells, can be irreversibly damaged, resulting in hearing loss and balance problems. These are known as ototoxic medications. People vary widely in their susceptibility to these agents as well as to damage caused by other chemical agents, loud sounds and aging.
To find out why this is so, senior scientists Edwin Rubel, David Raible, and their research team developed a screening strategy that uses hair cells in the lateral line of zebrafish larvae to signal how hair cells in a person's inner ear might respond under similar conditions. Hair cells are named for small bristly extensions, or stereocilia, jutting from their tops. Movement of fluid (triggered by sound vibrations in the inner ear or changes in water pressure in the fish's environment) causes the stereocilia to tilt to one side, generating an electrical impulse that travels to the brain.
The researchers first set out to identify genes that may be involved in how hair cells respond to ototoxic medicines. Using a chemical that causes random mutations in zebrafish, the researchers bred various fish families, with each family exhibiting a different set of mutations. The researchers then exposed five-day-old larval offspring to the drug neomycin, a type of antibiotic that damages these hair cells as well as those in the human inner ear. The larvae were then stained to determine if the hair cells were still intact. Fish that were resistant to damage were quickly identified as were those that were especially vulnerable.