title: Oncomodulin links inflammation to optic nerve regeneration.
abstract: The inflammatory response that accompanies central nervous system (CNS) injury can affect neurological outcome in both positive and negative ways. In the optic nerve, a CNS pathway that normally fails to regenerate when damaged, intraocular inflammation causes retinal ganglion cells (RGCs) to switch into an active growth state and extend lengthy axons down the nerve. The molecular basis of this phenomenon is uncertain. A prior study showed that oncomodulin (Ocm), a Ca(2+)-binding protein secreted by a macrophage cell line, is a potent axon-promoting factor for RGCs. However, it is not known whether Ocm contributes to the physiological effects of intraocular inflammation in vivo, and there are conflicting reports in the literature regarding its expression and significance. We show here 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. These results were verified in different strains, species, and experimental models, and establish Ocm as a potent growth-promoting signal between the innate immune system and neurons in vivo.
authors.affiliation: Department of Surgery and Anesthesiology, Children's Hospital, Laboratory for Neuroscience Research in Neurosurgery, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Yin
authors.forename: Qi
authors.initials: Q
authors.lastname: Cui
authors.forename: Hui-Ya
authors.initials: HY
authors.lastname: Gilbert
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yang
authors.forename: Cynthia
authors.initials: C
authors.lastname: Berlinicke
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.forename: Camila
authors.initials: C
authors.lastname: Zaverucha-do-Valle
authors.forename: Huamei
authors.initials: H
authors.lastname: He
authors.forename: Victoria
authors.initials: V
authors.lastname: Petkova
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Zack
authors.forename: Larry I
authors.initials: LI
authors.lastname: Benowitz
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration; D009900:Optic Nerve / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
chemical_list: D002135:Calcium-Binding Proteins; C034733:oncomodulin