Nature Neuroscience 9, 843 - 852 (2006)
Published online: 14 May 2006; | doi:10.1038/nn1701
Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cellsYuqin Yin1, 2, Michael T Henzl3, Barbara Lorber1, 2, Toru Nakazawa1, 4, Tommy T Thomas5, Fan Jiang1, Robert Langer5
& Larry I Benowitz1, 2, 61
Department of Neurosurgery and Neurobiology Program, Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA. 2
Department of Surgery, Harvard Medical School, Boston, Massachusetts 02115, USA. 3
Department of Biochemistry, 117 Schweitzer Hall, University of Missouri, Columbia, Missouri 65211, USA. 4
Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02115, USA. 5
Department of Chemical and Biomedical Engineering, E-25, Massachusetts Institute of Technology, Cambridge, Massachusetts 03139, USA. 6
Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA.
Correspondence should be addressed to Larry I Benowitz larry.benowitz@childrens.harvard.edu 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 (Ca2+)-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 Ca2+/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.
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