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Nerve endings: In mice, it is hard to see nerves that descend into a tumor under normal light (left, in blue). But when the mice are injected with a nerve-specific fluorescent probe, the buried branches are easier to see (middle). Combined with a tumor probe, the approach can highlight both the tumor to be removed (right, in green) and the nerves to be spared.
Credit: Michael A. Whitney et al

Nerves Light Up to Warn Surgeons Away

Tagging nerves with fluorescent markers could help surgeons avoid harming them.

• Monday, February 14, 2011
• By Courtney Humphries

Surgeons take pains to avoid injuring nerves in and around surgical sites—a stray cut could lead to muscle weakness, pain, numbness, or even paralysis. In delicate operations like prostate removal, for instance, accidentally damaging nerves can lead to incontinence or erectile dysfunction. Scientists at University of California San Diego have announced a new method for lighting up nerves in the body with fluorescent peptides, which could act as markers to keep surgeons away.

Quyen Nguyen, a surgeon at UCSD who led the research, says that during their training, surgeons learn where nerves are located and use that knowledge to avoid them. Most of the time, knowledge and experience are enough, but if anything is out of place or damaged for some reason, "finding the nerves can be challenging," Nguyen says. Fluorescence offers a way to let surgeons see them "even before they encounter them with their tools," she says.

Nguyen, working with chemist Roger Tsien, has previously created fluorescent markers that can illuminate the margins of tumors during surgery. To identify a specific tag for nerves, her team used a technique called phage display. A phage is a virus that infects bacteria, and it displays a small protein on its surface called a coat. Scientists can easily change the sequence of amino acids of this protein, creating millions of phages that display different coats. Using this technique, Nguyen's team looked for sequences of amino acids that preferentially stuck to nerve cells, and used that information to design a peptide that can serve as a nerve-specific tag. By adding a fluorescent probe to the peptide, they created a beacon that illuminates nerves under a particular wavelength of light.

The researchers injected their peptide into the bloodstream of mice, and found that all peripheral nerves (those outside the brain and spinal cord) were labeled within two hours. The effect lasted for several hours, and was completely gone after a day. The label worked even if nerves were damaged. The researchers also tested the peptide in human tissue samples and confirmed that it would also bind to human nerves.

These probes could be used in concert with probes for cancer, helping a surgeon to remove a tumor while avoiding the nerves around it. The technology has been licensed by Avelas Biosciences, a small biotech startup cofounded by Tsien; further animal testing will be needed before it's ready for clinical studies.

Hisataka Kobayashi, chief scientist in the Molecular Imaging Program at the National Cancer Institute, says that "there's no question this is a great technology" that has the potential to benefit surgeons. But he says the researchers will need to identify the exact molecular target of the probes and verify that they are completely nontoxic.