Oncomodulin links inflammation to optic nerve regeneration.
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.
Yin
Yuqin
Y
Department of Surgery and Anesthesiology, Children's Hospital, Laboratory for Neuroscience Research in Neurosurgery, Harvard Medical School, Boston, MA 02115, USA.
Cui
Qi
Q
Gilbert
Hui-Ya
HY
Yang
Yang
Y
Yang
Zhiyong
Z
Berlinicke
Cynthia
C
Li
Zhiwei
Z
Zaverucha-do-Valle
Camila
C
He
Huamei
H
Petkova
Victoria
V
Zack
Donald J
DJ
Benowitz
Larry I
LI
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
D002135:Calcium-Binding Proteins; C034733:oncomodulin