Inner Ear Undertakers

Support cells in the inner ear respond differently to two drugs that kill hair cells.

Sep 1, 2015
Kerry Grens

EDITOR'S CHOICE IN CELL & MOLECULAR BIOLOGY

CORPSE REMOVAL: An inner ear supporting cell (green) engulfs a dying hair cell (red) in the sensory epithelium of a mouse utricle.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.

Killer drugs
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.

Body bags
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.

Spilled guts
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.

Distress call
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.”