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These Peptides Have Got a Lot of Nerve

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Science Translational Medicine  02 Mar 2011:
Vol. 3, Issue 72, pp. 72ec29
DOI: 10.1126/scitranslmed.3002295

Surgeons are an ocular phenotype; in other words, they have to be able to see to operate. The ability to better visualize an organ or tissue within the body is therefore an ongoing stimulus for innovation and discovery in the biomedical sciences. For instance, one complication during peripheral nerve surgery is inadvertent transection or injury, which can result in chronic pain, paralysis, or even death of the patient. Whitney and colleagues enlighten us with an elegant solution to this surgical problem: Make the nerves fluoresce. To this end, the authors describe the selection through phage display technology of several short (11 to 12 amino acids) peptides that preferentially bind to peripheral mouse nerve tissue instead of adjacent nonnerve tissue, such as muscle. The peptides were then labeled with a fluorescein moiety, which permitted fluorescence imaging of peripheral motor and sensory nerves in vivo in mice, 2 to 4 hours after injection into their veins. Even tiny, 50-µm nerve branches, called arborizations, fluoresced brightly; notably, the smallest human nerve that would require imaging during surgery is an order of magnitude larger than this. The authors were also able to image in vivo the nerves buried beneath a breast cancer tumor—a location that is practically invisible during standard illumination procedures.

Highlighting the translational nature of this research, the authors demonstrate that an optimized fluorescent peptide, named NP41, can recognize and bind to freshly resected nerves ex vivo in human laryngeal tissue samples. The peptide is also cleared from the system after 24 hours via natural metabolism, thus indicating its potential biocompatibility (lack of toxicity) in a human patient. Reduction in accidental injury and death during surgery has far-reaching implications, which span from the bench to the clinic. The nerve-illuminating technology introduced by Whitney et al. has the potential to aid in very complex surgical procedures, such as limb reattachment and tumor resection, thus avoiding harmful or morbid outcomes and improving overall patient care.

M. A. Whitney et al., Fluorescent peptides highlight peripheral nerves during surgery in mice. Nat. Biotechnol. 6 February 2011 (10.1038/nbt.1764). [Abstract]

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