Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells

Yuqin Yin, Michael T Henzl, Barbara Lorber, Toru Nakazawa, Tommy T Thomas, Fan Jiang, Robert Langer, Larry I Benowitz

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The optic nerve, like most mature CNS pathways, does not regenerate after injury. Through unknown mechanisms, however, macrophage activation in the eye stimulates retinal ganglion cells (RGCs) to regenerate long axons beyond the site of optic nerve injury. Here we identify the calcium (Ca(2+))-binding protein oncomodulin as a potent macrophage-derived growth factor for RGCs and other neurons. Oncomodulin binds to rat RGCs with high affinity in a cyclic AMP (cAMP)-dependent manner and stimulates more extensive outgrowth than other known trophic agents. Depletion of oncomodulin from macrophage-conditioned media (MCM) eliminates the axon-promoting activity of MCM. The effects of oncomodulin involve downstream signaling via Ca(2+)/calmodulin kinase and gene transcription. In vivo, oncomodulin released from microspheres promotes regeneration in the mature rat optic nerve. Oncomodulin also stimulates outgrowth from peripheral sensory neurons. Thus, oncomodulin is a new growth factor for neurons of the mature central and peripheral nervous systems.

Original languageEnglish
Pages (from-to)843-52
Number of pages10
JournalNature neuroscience
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 2006
Externally publishedYes

Keywords

  • Oncomodulin
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Axons
  • Cells, Cultured
  • Macrophages
  • Nerve Regeneration
  • Optic Nerve
  • Retinal Ganglion Cells
  • Signal Transduction

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    Yin, Y., Henzl, M. T., Lorber, B., Nakazawa, T., Thomas, T. T., Jiang, F., ... Benowitz, L. I. (2006). Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nature neuroscience, 9(6), 843-52. https://doi.org/10.1038/nn1701