Optogenetic stimulation could treat laryngeal paralysis

Optogenetics can stimulate the larynx muscles of mice, which could someday be an option for treating laryngeal paralysis.

Content Dam Bow Online Articles 2015 June Sasse 2 Web

Researchers at the University of Bonn (Germany) have found a way to stimulate the larynx muscles of mice using optogenetics, which could someday be an option for treating laryngeal paralysis, a condition that causes difficulties in phonation and breathing.

Related: Laser pulses remove cancers of the larynx

Muscles respond to nerve stimulation by contracting. Normally, light cannot be used to initiate these contractions. But optogenetics uses a group of molecules known as channelrhodopsins (ion channels that open when illuminated) that, when appropriately packaged and injected into a muscle, integrate into individual muscle cells. As soon as these cells are exposed to light, the channels open and positively charged ions flow into the muscle cell, which then contracts.

In 2010, the researchers used optogenetics to stimulate the heart in mice. However, laryngeal muscles are part of the skeletal musculature, "and skeletal muscles follow different rules," says Dr. Philipp Sasse, who led the work. For instance, each fiber in a skeletal muscle can contract separately, which allows to control movements as well as muscle strength precisely. In addition, unlike heart muscle, skeletal muscles can perform static contractions if they are repeatedly stimulated at high frequency. "For the first time, we have been able to show that light pulses can also create static contractions," says Dr. Tobias Bruegmann, the first author on the study. "Depending on where we point the light beam, we can also stimulate individual muscle groups--exactly the same way the body does it through the nerves."

Content Dam Bow Online Articles 2015 June Sasse 2 Web
(L-R) Dr. Tobias Bruegmann, Dr. Philipp Sasse, and Dr. Tobias van Bremen use an optical fiber to demonstrate the functional principle. (Photo: Claudia Siebenhuener/University Hospital Bonn)

As a result, the method may point the way to new treatment approaches. In a few years, for instance, people with laryngeal paralysis could benefit from it. Laryngeal paralysis can occur after thyroid operations and during other pathological processes that affect the laryngeal nerves. The larynx plays an important role in speaking and swallowing, but most importantly in breathing: when you breathe, the muscles of the larynx pull the vocal cords apart so that air can flow into the lungs. In the event of complete paralysis, the patient can no longer breathe.

Unfortunately, electrical stimulators aren't all that effective in restoring larynx function "because there are different muscles with opposite function close together," explains Dr. Tobias van Bremen, an ear, nose, and throat doctor and one of the co-authors of the study. "It is almost impossible to stimulate these muscles individually using electrodes."

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The functional principle: the rear laryngeal muscles are genetically modified so that they open the air passage when exposed to light. (Courtesy of Dr. Tobias Bruegmann)

The researchers have shown that the method works in animals, as they were able to use light to open the air passage in the larynges of mice. However, several technical hurdles have to be overcome, such as bringing the channelrhodopsin into the larynx musculature. The researchers are currently testing gene transfer techniques and also optical stimulators.

Full details of the work appear in the journal Nature Communications; for more information, please visit http://dx.doi.org/10.1038/ncomms8153.

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