Axon regeneration in goldfish and rat retinal ganglion cells: differential responsiveness to carbohydrates and cAMP.
Mammalian retinal ganglion cells (RGCs) do not normally regenerate their axons through an injured optic nerve, but can be stimulated to do so by activating macrophages intraocularly. In a cell culture model of this phenomenon, we 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. In lower vertebrates, RGCs regenerate their axons spontaneously in vivo, and in culture, the most potent axon-promoting factor for these cells is a molecule that resembles the small vitreous-derived growth factor from the rat. This molecule was isolated chromatographically and was shown by mass spectrometry to be a carbohydrate. In agreement with this finding, D-mannose proved to be a potent axon-promoting factor for rat RGCs (ED50 approximately 10 microm); this response was cAMP-dependent and was augmented further by macrophage-derived proteins. Goldfish RGCs showed far less selectivity, responding strongly to either D-mannose or D-glucose in a cAMP-independent manner. These findings accord well with the success or failure of optic nerves to regenerate in higher and lower vertebrates in vivo. The axon-promoting effects of mannose are highly specific and are unrelated to energy metabolism or glycoprotein synthesis.
Li
Yiming
Y
Laboratories for Neuroscience Research in Neurosurgery, Children's Hospital, Boston, Massachusetts 02115, USA.
Irwin
Nina
N
Yin
Yuqin
Y
Lanser
Marc
M
Benowitz
Larry I
LI
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002241:Carbohydrates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D006054:Goldfish; D008264:Macrophages / Q000737:chemistry; D008297:Male; D008358:Mannose / Q000494:pharmacology; D013058:Mass Spectrometry; D009414:Nerve Growth Factors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009416:Nerve Regeneration; D009457:Neuroglia / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014822:Vitreous Body / Q000166:cytology
D002241:Carbohydrates; D009414:Nerve Growth Factors; D000242:Cyclic AMP; D008358:Mannose