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The Journal of Neuroscience, August 27, 2003, 23(21):7830-7838

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Axon Regeneration in Goldfish and Rat Retinal Ganglion Cells: Differential Responsiveness to Carbohydrates and cAMP

Yiming Li,^1,2 * Nina Irwin,^1,2 * Yuqin Yin,^1,2 * Marc Lanser,⁴ and Larry I. Benowitz^1,2,3

¹Laboratories for Neuroscience Research in Neurosurgery, Children's Hospital, ²Department of Surgery, and ³Program in Neuroscience, Harvard Medical School, and ⁴Boston Life Sciences, Inc., Boston, Massachusetts 02115

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 10 µM); 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.

Key words: retina; optic nerve; axon; regeneration; retinal ganglion cells; mannose; growth factors; macrophages; cAMP

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Received March 4, 2003; revised July 7, 2003; accepted July 8, 2003.

This article has been cited by other articles:

				T. Liedtke, J. C. Schwamborn, U. Schroer, and S. Thanos Elongation of Axons during Regeneration Involves Retinal Crystallin {beta} b2 (crybb2) Mol. Cell. Proteomics, May 1, 2007; 6(5): 895 - 907. [Abstract] [Full Text] [PDF]

				V. Pernet and A. Di Polo Synergistic action of brain-derived neurotrophic factor and lens injury promotes retinal ganglion cell survival, but leads to optic nerve dystrophy in vivo Brain, April 1, 2006; 129(4): 1014 - 1026. [Abstract] [Full Text] [PDF]

				D. Fischer, V. Petkova, S. Thanos, and L. I. Benowitz Switching Mature Retinal Ganglion Cells to a Robust Growth State In Vivo: Gene Expression and Synergy with RhoA Inactivation J. Neurosci., October 6, 2004; 24(40): 8726 - 8740. [Abstract] [Full Text] [PDF]

				D. Fischer, Z. He, and L. I. Benowitz Counteracting the Nogo Receptor Enhances Optic Nerve Regeneration If Retinal Ganglion Cells Are in an Active Growth State J. Neurosci., February 18, 2004; 24(7): 1646 - 1651. [Abstract] [Full Text] [PDF]

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