Abstract
Nerve preservation is an important goal during surgery because accidental transection or injury leads to significant morbidity, including numbness, pain, weakness or paralysis. Nerves are usually identified by their appearance and relationship to nearby structures or detected by local electrical stimulation (electromyography), but thin or buried nerves are sometimes overlooked. Here, we use phage display to select a peptide that binds preferentially to nerves. After systemic injection of a fluorescently labeled version of the peptide in mice, all peripheral nerves are clearly delineated within 2 h. Contrast between nerve and adjacent tissue is up to tenfold, and useful contrast lasts up to 8 h. No changes in behavior or activity are observed after treatment, indicating a lack of obvious toxicity. The fluorescent probe also labels nerves in human tissue samples. Fluorescence highlighting is independent of axonal integrity, suggesting that the probe could facilitate surgical repair of injured nerves and help prevent accidental transection.
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Acknowledgements
We are indebted to members of our laboratory for discussions and comments on the manuscript. Results described here are being used in support of a patent filing by the University of California, San Diego. This work was supported by the Howard Hughes Medical Institute, grants from the Burrough-Wellcome Fund (Career Award for Medical Scientists) and National Institutes of Health (NIH, 5K08EB008122) to Q.T.N. and NIH grant NS27177 to R.Y.T.
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M.A.W. designed and performed experiments, interpreted data and wrote manuscript. J.L.C. designed and performed experiments and interpreted data. L.T.N. designed and performed experiments and interpreted data. B.F. designed and performed experiments and interpreted data. L.A.G. designed and performed experiments and interpreted data. P.S. provided computer support for experiments, R.Y.T. designed experiments, interpreted data and wrote manuscript. Q.T.N. designed and performed experiments, interpreted data and wrote manuscript.
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M.A.W., R.Y.T. and Q.T.N. are scientific advisors for Avelas Biosciences, Inc., who has licensed the technology described above from the University of California San Diego.
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Whitney, M., Crisp, J., Nguyen, L. et al. Fluorescent peptides highlight peripheral nerves during surgery in mice. Nat Biotechnol 29, 352–356 (2011). https://doi.org/10.1038/nbt.1764
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DOI: https://doi.org/10.1038/nbt.1764
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