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

  title={Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells},
  author={Yuqin Yin and Michael T. Henzl and Barbara Lorber and Toru Nakazawa and Tommy T. Thomas and Fan Jiang and Robert Langer and Larry I. Benowitz},
  journal={Nature Neuroscience},
The optic nerve, like most mature CNS pathways, does not regenerate after injury. [] Key Result 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…
Oncomodulin derived from regeneration-associated macrophages in dorsal root ganglia after preconditioning injury promotes sensory axon regeneration in the spinal cord
It is reported that oncomodulin (ONCM) is an effector molecule derived from regeneration-associated macrophages and NG-mediated ONCM delivery could be exploited as a therapeutic strategy for promoting sensory axon regeneration following spinal cord injury.
Long-Distance Axon Regeneration in the Mature Optic Nerve: Contributions of Oncomodulin, cAMP, and pten Gene Deletion
It is shown that the induction of a controlled inflammatory response in the eye, when combined with elevation of intracellular cAMP and deletion of the gene encoding pten, enables RGCs to regenerate axons the full length of the optic nerve in mature mice.
Neutrophils Express Oncomodulin and Promote Optic Nerve Regeneration
It is shown here that neutrophils, the first responders of the innate immune system, play a central role in inflammation-induced regeneration and can promote axon regeneration in the CNS.
Oncomodulin links inflammation to optic nerve regeneration
It is shown that intraocular inflammation causes infiltrative cells of the innate immune system to secrete high levels of Ocm, and that agents that prevent Ocm from binding to its receptor suppress axon regeneration.
Artemin augments survival and axon regeneration in axotomized retinal ganglion cells
Artemin/GFRα3, but not other GDNF family members, may be of value for optic nerve regeneration in mature mammals because of its effect on axon regeneration in RGCs both in vivo and in vitro.
Reaching the brain: Advances in optic nerve regeneration


Counteracting the Nogo Receptor Enhances Optic Nerve Regeneration If Retinal Ganglion Cells Are in an Active Growth State
It is concluded that gene therapy is an effective approach to enhancing axon regeneration in the CNS and that inactivation of NgR functioning greatly enhances axon Regeneration provided the intrinsic growth program of neurons is activated.
Macrophage-Derived Factors Stimulate Optic Nerve Regeneration
It is shown here that factors secreted by macrophages stimulate RGCs to regenerate their axons, and the effects of macrophage activation can be optimized by the timing of their activation.
Axon Regeneration in Goldfish and Rat Retinal Ganglion Cells: Differential Responsiveness to Carbohydrates and cAMP
It is found that a small molecule that is constitutively present in the vitreous, acting in concert with macrophage-derived proteins, stimulates mature rat RGCs to regenerate their axons if intracellular cAMP is elevated.
Lens Injury Stimulates Axon Regeneration in the Mature Rat Optic Nerve
Macrophage activation appears to play a key role, because intraocular injections of Zymosan, a yeast cell wall preparation, stimulated monocytes in the absence of lens injury and induced RGCs to regenerate their axons into the distal optic nerve.
Switching Mature Retinal Ganglion Cells to a Robust Growth State In Vivo: Gene Expression and Synergy with RhoA Inactivation
The results show that, with appropriate stimulation, mature CNS neurons can undergo dramatic changes in gene expression comparable with those seen in regenerating neurons of the PNS, and that RhoA inactivation by itself results in moderate regeneration, and strongly potentiates axon regeneration through the mature optic nerve when the growth state of neurons is activated.
Inflammation near the nerve cell body enhances axonal regeneration
  • X. Lu, P. Richardson
  • Biology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1991
It is concluded that changes favorable to axonal regeneration can be induced by products of inflammatory cells acting in the vicinity of the nerve cell body.
Inactivation of Rho Signaling Pathway Promotes CNS Axon Regeneration
It is reported that injured axons regrow directly on complex inhibitory substrates when Rho GTPase is inactivated, indicating that targeting signaling mechanisms converging to Rho stimulates axon regeneration on inhibitory CNS substrates.
TrkB Gene Transfer Protects Retinal Ganglion Cells from Axotomy-Induced Death In Vivo
Data provide proof-of-principle that enhancing the capacity of injured neurons to respond to trophic factors can be an effective neuroprotective strategy in the adult CNS.