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.
Using genetic techniques, the group then examined the larvae’s DNA, searching for segments that were closely tied to the desired property. In doing so, they zoomed in on five mutations—each located on different genes—that, when inherited from each parent, protected against hair cell damage. Further examination revealed that one of the identified genes corresponds to a gene that is also found in other vertebrates, including humans. Another five mutations were identified that offer protection under more complex genetic conditions.
Next, the team investigated whether they could identify chemical compounds that protect hair cells against ototoxic medicines. Using the same screening technique—exposing five-day-old zebrafish larvae to neomycin and later applying special stains to the hair cells—the researchers screened more than 10,000 compounds and narrowed them down to two similar chemicals that provide robust protection of hair cells against the neomycin. One of the compounds was later found to protect hair cells from a mouse’s inner ear against the drug, indicating that the same compound may be protective for other mammals as well.
“One of the pluses about working with zebrafish is that, like other fish, they produce hundreds of offspring. We can look at lots of animals and we can look at many hair cells per animal, which means that we can get good quantitative data,” said Dr. Raible.
The authors suggest that their research technique, which combines chemical screening with traditional genetic approaches, offers a fast and efficient way to identify potential drugs and drug targets that may one day provide therapies for people with hearing loss and balance disorders.
Other sponsors of the study include the American Academy of Otolaryngology—Head and Neck Surgery Foundation, the University of Washington Royalty Research Fund and the V.M. Bloedel Hearing Research Center.
Andrew Hyde | alfa
New way to look at cell membranes could change the way we study disease
19.11.2018 | University of Oxford
Controlling organ growth with light
19.11.2018 | European Molecular Biology Laboratory
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
19.11.2018 | Materials Sciences
19.11.2018 | Information Technology
19.11.2018 | Life Sciences