In general, neurons in the mature vertebrate central nervous system fail to regenerate after injury. Intriguingly, however, activation of macrophages in the eye after damage to the optic nerve stimulates the regeneration of retinal ganglion cells (RGCs), so that their axons grow beyond the site of injury. Yin et al., who previously determined that macrophage-secreted proteins less than 20 kD in size promoted axon regeneration, used mass spectrometry of a prominent component and identified oncomodulin, a calcium-binding protein that has been found in tumors. Although inactive on its own, oncomodulin potentiated the ability of mannose plus forskolin (which elevates cAMP levels) to promote axon outgrowth in cultured RGCs. Pharmacological analysis indicated that oncomodulin activity depended on Ca2+/calmodulin-dependent kinase II and on gene transcription. Delivery of oncomodulin and a cAMP analog into the vitreous promoted optic nerve regeneration in vivo. Thus, oncomodulin appears to represent a previously unidentified macrophage-derived trophic factor capable of promoting axonal regeneration in at least some central neurons. — EMA
Nat. Neurosci. 9, 843 (2006).