EDITOR'S CHOICE IN CELL & MOLECULAR BIOLOGY
ELYSSA MONZACK The paper
E.L. Monzack et al., “Live imaging the phagocytic activity of inner ear supporting cells in response to hair cell death,” Cell Death Differ, doi:10.1038/cdd.2015.48, 2015.
A number of commonly used medications can cause hearing loss by killing off cochlear hair cells, which translate sound waves into neural activity. To understand how they die, Lisa Cunningham and Elyssa Monzack of the National Institute on Deafness and Other Communication Disorders and colleagues turned to the utricle, a vestibular inner-ear structure involved with balance whose hair cells are very similar to those in the cochlea, which are notoriously resistant to culturing when mature.
The team developed a method to watch hair cells of whole mouse utricles die in real time after exposure to the chemotherapy drug cisplatin or the antibiotic neomycin. In response to the latter, supporting cells, glia-like neighbors of hair cells, appeared to form a phagosome around the corpses and engulf them. “You can see two, three, sometimes four supporting cells advancing simultaneously on that hair cell corpse,” says Cunningham—which suggests that the dying cell is giving off a specific and local signal.
In contrast, cisplatin-induced hair cell death provoked hardly any phagocytic reaction from supporting cells, about half of which themselves succumbed. Cunningham says this could have clinical implications if dead hair cells then spill their cytoplasmic contents into the tissue, which can result in an immune response that can cause even further damage.
Mark Warchol of Washington University in St. Louis says it will be important to identify the signal supporting cells are responding to after neomycin treatment. “There’s some molecular signal by which the hair cell causes [supporting cells] to execute this process. And with cisplatin, they’re just not capable of doing it.”