title: Intravitreal macrophage activation enables cat retinal ganglion cells to regenerate injured axons into the mature optic nerve.
abstract: In mature mammals, retinal ganglion cells (RGCs) are generally unable to regenerate injured axons into the optic nerve. Here, we report that an intravitreal injection of either of two macrophage activators, oxidized galectin-1 or zymosan, strongly enhanced the regeneration of transected RGC axons beyond an optic nerve crush site in adult cats. Using WGA-HRP as an anterograde tracer, we found that injection of either macrophage activator caused many axons to grow into the distal optic nerve when evaluated 14 days later, with the strongest effects seen after injecting 100 ng of galectin-1. Elongation continued for at least another 2 weeks. Control eyes injected with saline contained very few labeled axons extending across the crush site. Elevation of intracellular cAMP levels using forskolin also enhanced regeneration beyond the crush site to some extent, but this treatment did not augment the effect of galectin-1 any further. These results indicate that RGCs of adult cats are capable of reverting to an active growth state and at least partially overcoming an inhibitory CNS environment as a result of intravitreal macrophage activation.
authors.affiliation: Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tokita
authors.forename: Hidenori
authors.initials: H
authors.lastname: Horie
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D002415:Cats; D005260:Female; D037483:Galectin 1 / Q000008:administration & dosage; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects / Q000276:immunology*; D009900:Optic Nerve / Q000276:immunology* / Q000473:pathology; D020221:Optic Nerve Injuries / Q000276:immunology / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000502:physiology*; D014822:Vitreous Body / Q000276:immunology*; D015054:Zymosan / Q000008:administration & dosage
chemical_list: D037483:Galectin 1; D015054:Zymosan