Journal Home > Volume 5 , Issue 1

Optic neuropathy refers to disorders involving the optic nerve (ON). Any damage to ON or ON-deriving neurons, the retinal ganglion cells (RGCs), may lead to the breakdown of the optical signal transmission from the eye to the brain, thus resulting in a partial or complete vision loss. The causes of optic neuropathy include trauma, ischemia, inflammation, compression, infiltration, and mitochondrial damages. ON injuries include primary and secondary injuries. During these injury phases, various factors orchestrate injured axons to die back and become unable to regenerate, and these factors could be divided into two categories: extrinsic and intrinsic. Extrinsic inhibitory factors refer to the environmental conditions that influence the regeneration of injured axons. The presence of myelin inhibitors and glial scar, lack of neurotrophic factors, and inflammation mediated by injury are regarded as these extrinsic factors. Extrinsic factors need to trigger the intracellular signals to exert inhibitory effect. Proper regulation of these intracellular signals has been shown to be beneficial to ON regeneration. Intrinsic factors of RGCs are the pivotal reasons that inhibit ON regeneration and are closely linked with extrinsic factors. Intracellular cyclic adenosine monophosphate (cAMP) and calcium levels affect axon guidance and growth cone response to guidance molecules. Many genes, such as Bcl-2, PTEN, and mTOR, are crucial in cell proliferation, axon guidance, and growth during development, and play important roles in the regeneration and extension of RGC axons. With transgenic mice and related gene regulations, robust regeneration of RGC axons has been observed after ON injury in laboratories. Although various means of experimental treatments such as cell transplantation and gene therapy have achieved significant progress in neuronal survival, axonal regeneration, and restoration of the visual function after ON injury, many unresolved scientific problems still exist for their clinical applications. Therefore, we still need to overcome hurdles before developing effective therapy to treat optic neuropathy diseases in patients.


menu
Abstract
Full text
Outline
About this article

Restoration of optic neuropathy

Show Author's information Si-Wei You1( )Ming-Mei Wu2Fang Kuang2Kin-Sang Cho3Kwok-Fai So4,5
Department of Ophthalmology, Xijing Hospital,
Institute of Neurosciences, The Fourth Military Medical University, Xi’an, China
Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
GHM Institute of CNS Regeneration, Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou,
Department of Ophthalmology, The State Key laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China

Abstract

Optic neuropathy refers to disorders involving the optic nerve (ON). Any damage to ON or ON-deriving neurons, the retinal ganglion cells (RGCs), may lead to the breakdown of the optical signal transmission from the eye to the brain, thus resulting in a partial or complete vision loss. The causes of optic neuropathy include trauma, ischemia, inflammation, compression, infiltration, and mitochondrial damages. ON injuries include primary and secondary injuries. During these injury phases, various factors orchestrate injured axons to die back and become unable to regenerate, and these factors could be divided into two categories: extrinsic and intrinsic. Extrinsic inhibitory factors refer to the environmental conditions that influence the regeneration of injured axons. The presence of myelin inhibitors and glial scar, lack of neurotrophic factors, and inflammation mediated by injury are regarded as these extrinsic factors. Extrinsic factors need to trigger the intracellular signals to exert inhibitory effect. Proper regulation of these intracellular signals has been shown to be beneficial to ON regeneration. Intrinsic factors of RGCs are the pivotal reasons that inhibit ON regeneration and are closely linked with extrinsic factors. Intracellular cyclic adenosine monophosphate (cAMP) and calcium levels affect axon guidance and growth cone response to guidance molecules. Many genes, such as Bcl-2, PTEN, and mTOR, are crucial in cell proliferation, axon guidance, and growth during development, and play important roles in the regeneration and extension of RGC axons. With transgenic mice and related gene regulations, robust regeneration of RGC axons has been observed after ON injury in laboratories. Although various means of experimental treatments such as cell transplantation and gene therapy have achieved significant progress in neuronal survival, axonal regeneration, and restoration of the visual function after ON injury, many unresolved scientific problems still exist for their clinical applications. Therefore, we still need to overcome hurdles before developing effective therapy to treat optic neuropathy diseases in patients.

Keywords: retinal ganglion cells, optic nerve injury, neuronal survival, axonal regeneration, vision restoration

References(129)

1.
Harvey AR, Hu Y, Leaver SG, et al. Gene therapy and transplantation in CNS repair: the visual system. Prog Retin Eye Res. 2006;25(5):449-489.
2.
Park KK, Liu K, Simth PD, et al. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science. 2008;322(5903):963-966.
3.
Smith PD, Park KK, Cai B, et al. SOCS3 deletion promotes optic nerve. Neuron. 2009;64(5):617-623.
4.
Cui Q, Cho KS, So KF, Yip HK. Synergistic effect of Nogo-neutralizing antibody IN-1 and ciliary neurotrophic factor on axonal regeneration in adult rodent visual systems. J Neurotrauma. 2004;21(5):617-625.
5.
Su Y, Wang F, Zhao SG, Pan SH, Liu P, Teng Y, Cui H. Axonal regeneration after optic nerve crush in Nogo-A/B/C knockout mice. Mol Vis. 2008;14:268-273.
6.
Su Y, Wang F, Teng Y, Zhao SG, Cui H, Pan SH. Axonal regeneration of optic nerve after crush in Nogo66 receptor knockout mice. Neurosci Lett. 2009;460(3):223-226.
7.
Fischer D, He Z, Benowitz LI. Counteracting the Nogo receptor enhances optic nerve regeneration if retinal ganglion cells are in an active growth state. J Neurosci. 2004;24(7):1646-1651.
8.
Chen C, Chen X, Yin X, Yuan R, Wang B, Ye J. NgR RNA interference, combined with zymosan intravitreal injection, enhances optic nerve regeneration. J Neurochem. 2009;110(5):1628-1634.
9.
Ahmed Z, Suggate EL, Brown ER, et al. Schwann cell-derived factor-induced modulation of the NgR/p75NTR/EGFR axis disinhibits axon growth through CNS myelin in vivo and in vitro. Brain. 2006;129(Pt 6):1517-1533.
10.
Abdesselem H, Shypitsyna A, Solis GP, Bodrikov V, Stuermer CA. No Nogo66-and NgR-mediated inhibition of regenerating axons in the zebrafish optic nerve. J Neurosci. 2009;29(49):15489-15498.
11.
Planchamp V, Bermel C, Tönges L, et al. BAG1 promotes axonal outgrowth and regeneration. Brain. 2008;131(Pt 10):2606-2619.
12.
Bartsch S, Montag D, Schachner M, Bartsch U. Increased number of unmyelinated axons. Brain Res. 1997;762(1-2):231-234.
13.
Dezawa M, Nagano T. Immunohistochemical localization of cell adhesion molecules and cell-cell contact proteins during regeneration of the rat optic nerve induced by sciatic nerve autotransplantation. Anat Rec. 1996;246(1):114-126.
DOI
14.
Li C, Tropak MB, Gerlai R, et al. Myelination in the absence of myelin. Nature. 1994;369(6483):747-750.
15.
Bartsch U. Myelination and axonal regeneration. J Neurocytol. 1996;25(5):303-313.
16.
Wong EV, David S, Jacob MH, Jay DG. Inactivation of myelin. J Neurosci. 2003;23(8):3112-3117.
17.
Xiao ZC, Bartsch U, Margolis RK, Rougon G, Montag D, Schachner M. Isolation of a tenascin-R binding protein from mouse brain. J Biol Chem. 1997;272(51):32092-32101.
18.
Pizz MA, Elam JS. Characterization of a chondroitin sultate proteoglycan associated with regeneration. Neurochem Res. 2004;29(4):719-728.
19.
Chung KY, Taylor JS, Shum DK, Chan SO. Axon routing at the optic chiasm. Development. 2000;127(12):2673-2683.
20.
Becker CG, Becker T. Repellent guidance. J Neurosci. 2002;22(3):842-853.
21.
Sellés-Navarro I, Ellezam B, Fajardo R, Latour M, McKerracher L. Retinal ganglion cell and nonneuronal cell responses to a microcrush lesion of adult rat optic nerve. Exp Neurol. 2001;167(2):282-289.
22.
Monnier PP, Sierra A, Schwab JM, Henke-Fahle S, Mueller BK. The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar. Mol Cell Neurosci. 2003;22(3):319-330.
23.
Kipnis J, Yoles E, Porat Z, et al. T cell immunity to copolymer 1 confers neuroprotection on the damaged optic nerve: Possible therapy for optic neuropathies. Proc Natl Acad Sci U S A. 2000;97(13):7446-7451.
24.
Schori H, Kipnis J, Yoles E, WoldeMussie E, Ruiz G, Wheeler LA, Schwartz M. Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: Implications for glaucoma. Proc Natl Acad Sci U S A. 2001;98(6):3398-3403.
25.
Ellezam B, Bertrand J, Dergham P, McKerracher L. Vaccination stimulates retinal ganglion cell regeneration in the adult optic nerve. Neurobiol Dis. 2003;12(1):1-10.
26.
Watanabe M, Sawai H, Fukuda Y. Survival of axotomized retinal ganglion cells in adult mammals. Clin Neurosci. 1997;4(5):233-239.
27.
Sawai H, Clarke DB, Kittlerova P, Bray GM, Aguayo AJ. Brain-derived neurotrophic factor and neurotrophin-4/5 stimulate growth of axonal branches from regenerating retinal ganglion cells. J Neurosci. 1996;16(12):3887-3894.
28.
Negishi H, Dezawa M, Oshitari T, Adachi-Usami E. Optic nerve regeneration within artificial Schwann cell graft in the adult rat. Brain Res Bull. 2001;55(3):409-419.
29.
Watanabe M, Tokita Y, Kato M, Fukuda Y. Intravitreal injections of neurotrophic factors and forskolin enhance survival and axonal regeneration of axotomized beta ganglion cells in cat retina. Neuroscience. 2003;116(3):733-742.
30.
Douglas MR, Morrison KC, Jacques SJ, et al. Off-target effects of epidermal growth factor receptor antagonists mediate retinal ganglion cell disinhibited axon growth. Brain. 2009;132(Pt 11):3102-3121.
31.
Caleo M, Menna E, Chierzi S, Cenni MC, Maffei L. Brain-derived neurotrophic factor is an anterograde survival factor in the rat visual system. Curr Biol. 2000;10(19):1155-1161.
32.
Kurokawa T, Katai N, Shibuki H, Kuroiwa S, Kurimoto Y, Nakayama C, Yoshimura N. BDNF diminishes caspase-2 but not c-Jun immunoreactivity of neurons in retinal ganglion cell layer after transient ischemia. Invest Ophthalmol Vis Sci. 1999;40(12):3006-3011.
33.
Kashiwagi F, Kashiwagi K, Iizuka Y, Tsukahara S. Effects of brain-derived neurotrophic factor and neurotrophin-4 on isolated cultured retinal ganglion cells: evaluation by flow cytometry. Invest Ophthalmol Vis Sci. 2000;41(8):2373-2377.
34.
Hirsch S, Labes M, Bähr M. Changes in BDNF and neurotrophin receptor expression in degenerating and regenerating rat retinal ganglion cells. Restor Neurol Neurosci. 2000;17(2):125-134.
35.
Kermer P, Klöcker N, Labes M, Bähr M. Insulin-like growth factor-I protects axotomized rat retinalganglion cells from secondary death via PI3-K-dependent Akt phosphorylation and inhibition of caspase-3 In vivo. J Neurosci. 2000;20(2):2-8.
36.
Peterson WM, Wang Q, Tzekova R, Wiegand SJ. Ciliary neurotrophic factor and stress stimuli activate the Jak-STAT pathway in retinal neurons and glia. J Neurosci. 2000;20(11):4081-4090.
37.
Weise J, Isenmann S, Klöcker N, Kügler S, Hirsch S, Gravel C, Bähr M. Adenovirus mediated expression of ciliary neurotrophic factor (CNTF) rescues axotomized rat retinal ganglion cells but does not support axonal regeneration in vivo. Neurobiol Dis. 2000;7(3):212-223.
38.
van Adel BA, Arnold JM, Phipps J, Doering LC, Ball AK. Ciliary neurotrophic factor protects retinal ganglion cells from axotomy-induced apoptosis via modulation of retinal glia in vivo. J Neurobiol. 2005;63(3):215-234.
39.
Ishikawa H, Takano M, Matsumoto N, Sawada H, Ide C, Mimura O, Dezawa M. Effect of GDNF genetransfer into axotomized retinal ganglion cells using in vivo electroporation with a contact lens-type electrode. Gene Ther. 2005;12(4):289-298.
40.
MacLaren RE, Buch PK, Smith AJ, et al. CNTF gene transfer protects ganglion cells in rat retinae undergoing focal injury and branch vessel occlusion. Exp Eye Res. 2006;83(5):1118-1127.
41.
Schuettauf F, Vorwerk C, Naskar R, et al. Adeno-associated viruses containing bFGF or BDNF are neuroprotective against excitotoxicity. Curr Eye Res. 2004;29(6):379-386.
42.
Wu MM, Fan DG, Tadmori I, et al. Death of axotomized retinal ganglion cells delayed after intraoptic nerve transplantation of olfactory ensheathing cells in adult rats. Cell Transplant. 2010;19(2):159-166.
43.
Wang T, Cong R, Yang H, Wu MM, Luo N, Kuang F, You SW. Neutralization of BDNF attenuates the in vitro protective effects of olfactory ensheathing cell-conditioned medium on scratch-insulted retinal ganglion cells. Cell Mol Neurobiol. 2011;31(3):357-364.
44.
Cui Q, So KF, Yip HK. Major biological effects of neurotrophic factors on retinal ganglion cells in mammals. Biol Signals Recept. 1998;7(4):220-226.
45.
Cui Q, Lu Q, So KF, Yip HK. CNTF, not other trophic factors, promotes axonal regeneration of axotomized retinal ganglion cells in adult hamsters. Invest Ophthalmol Vis Sci. 1999;40(3):760-766.
46.
Logan A, Ahmed Z, Baird A, Gonzalez AM, Berry M. Neurotrophic factor synergy is required for neuronalsurvival and disinhibited axon regeneration after CNS injury. Brain. 2006;129(Pt 2):490-502.
47.
Mansour-Robaey S, Clarke DB, Wang YC, Bray GM, Aguayo AJ. Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. Proc Natl Acad Sci U S A. 1994;91(5):1632-1636.
48.
Fischer D, Heiduschka P, Thanos S. Lens-injury-stimulated axonal regeneration throughout the optic pathway of adult rats. Exp Neurol. 2001;172(2):257-272.
49.
Heiduschka P, Fischer D, Thanos S. Recovery of visual evoked potentials after regeneration of cut retinal ganglion cell axons within the ascending visual pathway in adult rats. Restor Neurol Neurosci. 2005;23(5-6):303-312.
50.
Leon S, Yin Y, Nguyen J, Irwin N, Benowitz LI. Lens injury stimulates axon regeneration in the mature rat optic nerve. J Neurosci. 2000;20(12):4615-4626.
51.
Yin Y, Cui Q, Li Y, Irwin N, Fischer D, Harvey AR, Benowitz LI. Macrophage-derived factors stimulate optic nerve regeneration. J Neurosci. 2003;23(6):2284-2293.10.1523/JNEUROSCI.23-06-02284.2003
52.
Irwin N, Li YM, O’Toole JE, Benowitz LI. Mst3b, a purine-sensitive Ste20-like protein kinase, regulates axon outgrowth. Proc Natl Acad Sci U S A. 2006;103(48):18320-18325.
53.
Lorber B, Berry M, Logan A. Different factors promote axonal regeneration of adult rat retinal ganglion cells after lens injury and intravitreal peripheral nerve grafting. J Neurosci Res. 2008;86(4):894-903.
54.
Li Y, Irwin N, Yin Y, Lanser M, Benowitz LI. Axon regeneration in goldfish and rat retinal ganglion cells: differential responsiveness to carbohydrates and cAMP. J Neurosci. 2003;23(21):7830-7838.
55.
Yin Y, Henzl MT, Lorber B, et al. Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nat Neurosci. 2006;9(6):843-852.
56.
Hauk TG, Müller A, Lee J, Schwendener R, Fischer D. Neuroprotective and axon growth promoting effects of intraocular inflammation do not depend on comodulin or the presence of large numbers of activated macrophages. Exp Neurol. 2008;209(2):469-482.
57.
Fischer D, Hauk TG, Müller A, Thanos S. Crystallins of the beta/gamma-superfamily mimic the effects of lens injury and promote axon regeneration. Mol Cell Neurosci. 2008;37(3):471-479.
58.
Leibinger M, Müller A, Andreadaki A, Hauk TG, Kirsch M, Fischer D. Neuroprotective and axon growth-promoting effects following inflammatory stimulation on mature retinal ganglion cells in mice depend on ciliary neurotrophic factor and leukemia inhibitory factor. J Neurosci. 2009;29(45):14334-14341.
59.
Müller A, Hauk TG, Fischer D. Astrocyte-derived CNTF switches mature RGCs to a regenerative state following inflammatory stimulation. Brain. 2007;130(Pt 2):3308-3320.
60.
Ying X, Zhang J, Wang Y, Wu N, Wang Y, Yew DT. Alpha-crystallin protected axons from optic nerve degeneration after crushing in rats. J Mol Neurosci. 2008;35(3):253-258.
61.
Urbina M, Schmeer C, Lima L. 5HT1A receptor agonist differentially increases cyclic AMP concentration in intact and lesioned goldfish retina. In vitro inhibition of outgrowth by forskolin. Neurochem Int. 1996;29(5):453-460.
62.
Höpker VH, Shewan D, Tessier-Lavigne M, Poo M, Holt C. Growth-cone attraction to netrin-1 is converted to repulsion by laminin-1. Nature. 1999;401(6748):69-73.
63.
Shewan D, Dwivedy A, Anderson R, Holt CE. Age-related changes underlie switch in netrin-1 responsiveness as growth cones advance along visual pathway. Nat Neurosci. 2002;5(10):955-962.
64.
Trousse F, Martí E, Gruss P, Torres M, Bovolenta P. Control of retinal ganglion cell axon growth: a new role for Sonic hedgehog. Development. 2001;128(20):3927-3936.
65.
Monsul NT, Geisendorfer AR, Han PJ, Banik R, Pease ME, Skolasky RL Jr, Hoffman PN. Intraocular injection of dibutyryl cyclic AMP promotes axon regeneration in rat optic nerve. Exp Neurol. 2004;186(2):124-133.
66.
Okada T, Ichikawa M, Tokita Y, Horie H, Saito K, Yoshida J, Watanabe M. Intravitreal macrophage activation enables cat retinal ganglion cells to regenerate injured axons into the mature optic nerve. Exp Neurol. 2005;196(1):153-163.
67.
Park KK, Luo JM, Hisheh S, Harvey AR, Cui Q. Cellular mechanisms associated with spontaneous and ciliary neurotrophic factor-cAMP-induced survival and axonal regeneration of adult retinal ganglion cells. J Neurosci. 2004;24(48):10806-10815.
68.
Rodger J, Goto H, Cui Q, Chen PB, Harvey AR. cAMP regulates axon outgrowth and guidance during optic nerve regeneration in goldfish. Mol Cell Neurosci. 2005;30(3):452-464.
69.
Miyoshi T, Kurimoto T, Fukuda Y. Attempts to restore visual function after optic nerve damage in adult mammals. Adv Exp Med Biol. 2006;557:133-147.
70.
Park KK, Hu Y, Muhling J, et al. Cytokine-induced SOCS expression is inhibited by cAMP analogue: impact on regeneration in injured retina. Mol Cell Neurosci. 2009;41(3):313-324.
71.
Hellström M, Muhling J, Ehlert EM, Verhaagen J, Pollett MA, Hu Y, Harvey AR. Negative impact of rAAV2 mediated expression of SOCS3 on the regeneration of adult retinal ganglion cell axons. Mol Cell Neurosci. 2011;46(2):507-515.
72.
Kashimoto R, Kurimoto T, Miyoshi T, et al. Cilostazol promotes survival of axotomized retinal ganglion cells in adult rats. Neurosci Lett. 2008;436(2):116-119.
73.
Saul KE, Koke JR, García DM. Activating transcription factor 3 (ATF3) expression in the neural retina and optic nerve of zebrafish during optic nerve regeneration. Comp Biochem Physiol A Mol Integr Physiol. 2010;155(2):172-182.
74.
Park KK, Liu K, Hu Y, Kanter JL, He Z. PTEN/mTOR and axon regeneration. Exp Neurol .2010;223(1):45-50.
75.
Huang X, Wu DY, Chen G, Manji H, Chen DF. Support of retinal ganglion cell survival and axon regeneration by lithium through a Bcl-2-dependent mechanism. Invest Ophthalmol Vis Sci. 2003;44(1):347-354.
76.
Schuettauf F, Rejdak R, Thaler S, et al. Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat. Exp Eye Res. 2006;83(5):1128-1134.
77.
Cho KS, Chen DF. Promoting optic nerve regeneration in adult mice with pharmaceutical approach. Neurochem Res. 2008;33(10):2126-2133.
78.
Yick LW, So KF, Cheung PT, Wu WT. Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury. J Neurotrauma. 2004;21(7):932-943.
79.
Li J, Khavandgar Z, Lin SH, Murshed M. Lithium chloride attenuates BMP-2 signaling and inhibits osteogenic differentiation through a novel WNT/GSK3-independent mechanism. Bone. 2011;48(2):321-331.
80.
Liu H, Thurig S, Mohamed O, Dufort D, Wallace VA. Mapping canonical Wnt signaling in the developing and adult retina. Invest Ophthalmol Vis Sci. 2006;47(11):5088-5097.
81.
Fragoso MA, Yi H, Nakamura RE, Hackam AS. The Wnt signaling pathway protects retinal ganglion cell 5 (RGC-5) cells from elevated pressure. Cell Mol Neurobiol. 2011;31(1):163-173.
82.
Seitz R, Hackl S, Seibuchner T, Tamm ER, Ohlmann A. Norrin mediates neuroprotective effects on retinal ganglion cells via activation of the Wnt/beta-catenin signaling pathway and the induction of neuroprotective growth factors in Muller cells. J Neurosci. 2010;30(17):5998-6010.
83.
So KF, Aguayo AJ. Lengthy regrowth of cut axons from ganglion cells after peripheral nerve transplantation into the retina of adult rats. Brain Res. 1985;328(2):349-354.
84.
Aoki H, Hara A, Niwa M, Motohashi T, Suzuki T, Kunisada T. Transplantation of cells from eye-like structures differentiated from embryonic stem cells in vitro and in vivo regeneration of retinal ganglion-like cells. Graefes Arch Clin Exp Ophthalmol. 2008;246(2):255-265.
85.
Hill AJ, Zwart I, Samaranayake AN, et al. Rat neurosphere cells protect axotomized rat retinal ganglion cells and facilitate their regeneration. J Neurotrauma. 2009;26(7):1147-1156.
86.
Charalambous P, Hurst LA, Thanos S. Engrafted chicken neural tube-derived stem cells support the innate propensity for axonal regeneration within the rat optic nerve. Invest Ophthalmol Vis Sci. 2008;49(8):3513-3524.
87.
Nishida A, Takahashi M, Tanihara H, et al. Incorporation and differentiation of hippocampus-derived neural stem cells transplanted in injured adult rat retina. Invest Ophthalmol Vis Sci. 2000;41(13):4268-4274.
88.
Tello F. La influencia del neurotropismo en la regeneraçion de los centros nerviosos [The influence of neurotropism on the regeneration of nerve centers]. Trab Lab Invest Bio. 1911;9:124-159. Spanish
89.
So KF, Xiao YM, Diao YC. Effects on the growth of damaged ganglion cell axons after peripheral nerve transplantation in adult hamsters. Brain Res. 1986;377(1):168-172.
90.
Wang R, Xu J, Xie J, et al. Hyperbaric oxygen preconditioning promotes survival of retinal ganglion cells in a rat model of optic nerve crush. J Neurotrauma. 2010;27(4):763-770.
91.
You SW, So KF, Yip HK. Axonal regeneration of retinal ganglion cells depending on the distance of axotomy in adult hamsters. Invest Ophthalmol Vis Sci. 2000;41(10):3165-3170.
92.
So KF, Yip HK. Axonal regeneration in the central nervous system. In: Ingoglia NA and Murray M, editors. The Use of Peripheral Nerve Transplants to Enhance Axonal Regeneration in CNS Neurons. New York, NY: Marcel Dekker, Inc. 2001;Chapter 20:505-528.
93.
You SW, Bedi KS, Yip HK, So KF. Axonal regeneration of retinal ganglion cells after optic nerve pre-lesions and attachment of normal or pre-degenerated peripheral nerve grafts. Vis Neurosci. 2002;19(5):661-668.
94.
Bray GM, Villegas-Pérez MP, Vidal-Sanz M, Aguayo AJ. The use of peripheral nerve grafts to enhanceneuronal survival, promote growth and permit terminal reconnections in the central nervous system of adult rats. J Exp Biol. 1987;132:5-19.
95.
Avilés-Trigueros M, Sauvé Y, Lund RD, Vidal-Sanz M. Selective innervation of retinorecipient brainstem nuclei by retinal ganglion cell axons regenerating through peripheral nerve grafts in adult rats. J Neurosci. 2000;20(1):361-374.
96.
Keirstead SA, Rasminsky M, Fukuda Y, Carte DA, Aguayo AJ, Vidal-Sanz M. Electrophysiologic responses in hamster superior colliculus evoked by regenerating retinal axons. Science. 1989;246(4927):255-257.
97.
Sauve Y, Gaillard F. Regeneration in the visual system of adult mammals. In: Kolb H, Fernandez E, Nelson R, editors. Webvision: The Organization of the Retina and Visual System (Internet). Salt Lake (UT): University of Utah Health Sciences Center; 1995.
98.
Dezawa M, Kawana K, Adachi-Usami E. The role of Schwann cells during retinal ganglion cell regeneration induced by peripheral nerve transplantation. Invest Ophthalmol Vis Sci. 1997;38(7):1401-1410.
99.
Maki H, Watanabe M, Tokita Y, Saito K, Yoshida J. Axons of alpha ganglion cells regenerate faster than other types into a peripheral nerve graft in adult cats. J Neurosci Res. 2003;72(2):218-226.
100.
Fukuda Y, Watanabe M. Regeneration of cat’s optic nerve and its functional recovery. Rev Bras Biol. 1996;56(Suppl 1 Pt 1):69-78.
101.
Hu Y, Leaver SG, Plan GW, et al. Lentiviral-mediated transfer of CNTF to Schwann cells within reconstructed peripheral nerve grafts enhances adult retinal ganglion cell survival and axonal regeneration. Mol Ther. 2005;11(6):906-915.
102.
You SW, Hellström M, Pollett MA, et al. Large-scale reconstitution of a retina-to-brain pathway in adult rats using gene therapy and bridging grafts: An anatomical and behavioral analysis. Exp Neurol. 2016;279:197-211.
103.
Raibon E, Sauvé Y, Carter DA, Gaillard F. Microglial changes accompanying the promotion of retinalganglion cell axonal regeneration into peripheral nerve grafts. J Neurocytol. 2002;31(1):57-71.
104.
Cui Q, Pollett MA, Symons NA, Plant GW, Harvey AR. A new approach to CNS repair using chimeric peripheral nerve grafts. J Neurotrauma. 2003;20(1):17-31.10.1089/08977150360517155
105.
Gillon RS, Cui Q, Dunlop SA, Harvey AR. Effects of immunosuppression on regrowth of adult rat retinal ganglion cell axons into peripheral nerve allografts. J Neurosci Res. 2003;74(4):524-532.
106.
Watanabe M. Regeneration of optic nerve fibers of adult mammals. Dev Growth Differ. 2010;52(7):567-576.
107.
Miller NR. Optic nerve protection, regeneration, and repair in the 21st century: LVIII Edward Jackson Memorial lecture. Am J Ophthalmol. 2001;132(6):811-818.
108.
Dahlmann-Noor A, Vijay S, Jayaram H, Limb A, Khaw PT. Current approaches and future prospects for stem cell rescue and regeneration of the retina and optic nerve. Can J Ophthalmol. 2010;45(4):333-341.
109.
Zwart I, Hill AJ, Al-Allaf F, et al. Umbilical cord blood mesenchymal stromal cells are neuroprotective and promote regeneration in a rat optic tract model. Exp Neurol. 2009;216(2):439-448.
110.
Johnson TV, Bull ND, Hunt DP, Marina N, Tomarev SI, Martin KR. Neuroprotective effects of intravitreal mesenchymal stem cell transplantation in experimental glaucoma. Invest Ophthalmol Vis Sci. 2010;51(4):2051-2059.
111.
Chen ZJ, Negra M, Levine A, Ughrin Y, Levine JM. Oligodendrocyte precursor cells: reactive cells that inhibit axon growth and regeneration. J Neurocytol. 2002;31(6-7):481-495.
112.
Bull ND, Irvine KA, Franklin RJ, Martin KR. Transplanted oligodendrocyte precursor cells reduce neurodegeneration in a model of glaucoma. Invest Ophthalmol Vis Sci. 2009;50(9):4244-4253.
113.
Dezawa M. Central and peripheral nerve regeneration by transplantation of Schwann cells and transdifferentiated bone marrow stromal cells. Anat Sci Int. 2002;77(1):12-25.
114.
Dai C, Qin YZ, Li Y, Raisman G, Li D. Survival of retinal ganglion cells in slice culture provides a rapid screen for olfactory ensheathing cell preparations. Brain Res. 2010;1354:40-46.
115.
Moreno-Flores MT, Lim F, Martín-Bermejo MJ, Díaz-Nido J, Avila J, Wandosell F. Immortalized olfactory ensheathing glia promote axonal regeneration of rat retinal ganglion neurons. J Neurochem. 2003;85(4):861-871.
116.
Sonigra RJ, Brighton PC, Jacoby J, Hall S, Wigley CB. Adult rat olfactory nerve ensheathing cells are effective promoters of adult central nervous system neurite outgrowth in coculture. Glia. 1999;25(3):256-269.
DOI
117.
Li Y, Sauvé Y, Li D, Lund RD, Raisman G. Transplanted olfactory ensheathing cells promote regeneration of cut adult rat optic nerve axons. J Neurosci. 2003;23(21):7783-7788.
118.
Li Y, Li D, Raisman G. Transplanted Schwann cells, not olfactory ensheathing cells, myelinate optic nerve fibres. Glia. 2007;55(3):312-316.
119.
Pastrana E, Moreno-Flores MT, Gurzov EN, Avila J, Wandosell F, Diaz-Nido J. Genes associated with adult axon regeneration promoted by olfactory ensheathing cells: a new role for matrix metalloproteinase 2. J Neurosci. 2006;26(20):5347-5359.10.1523/JNEUROSCI.1111-06.2006
120.
Hayat S, Thomas A, Afshar F, Sonigra R, Wigley CB. Manipulation of olfactory ensheathing cell signaling mechanisms: effects on their support for neurite regrowth from adult CNS neurons in coculture. Glia .2003;44(3):232-241.
121.
Leaver SG, Harvey AR, Plant GW. Adult olfactory ensheathing glia promote the long-distance growth of adult retinal ganglion cell neuritis in vitro. Glia. 2006;53(5):467-476.
122.
Wang YZ, Meng JH, Yang H, Luo N, Jiao XY, Ju G. Differentiation-inducing and protective effects of adult rat olfactory ensheathing cell conditioned medium on PC12 cells. Neurosci Lett. 2003;346(1-2):9-12.
123.
Feng L, Meng H, Wu F, et al. Olfactory ensheathing cells conditioned medium prevented apoptosis. Int J Dev Neurosci. 2008;26(3-4):323-329.
124.
Pellitteri R, Spatuzza M, Russo A, Stanzani S. Olfactory ensheathing cells exert a trophic effect on the hypothalamic neurons. Neurosci Lett. 2007;417(1):24-29.
125.
Vukovic J, Plant GW, Ruitenberg MJ, Harvey AR. Influence of adult Schwann cells and olfactory ensheathing glia. Neuron Glia Biol. 2007;3(2):105-117.
126.
Li Y, Li D, Khaw PT, Raisman G. Transplanted olfactory ensheathing cells incorporated into the optic nerve head ensheathe retinal ganglion cell axons: possible relevance to glaucoma. Neurosci Lett. 2008;440(3):251-254.
127.
Kauper K, McGovern C, Sherman S, et al. Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases. Invest Ophthalmol Vis Sci. 2012;53(12):7484-7491.
128.
Schwartz SD, Hubschman JP, Heilwell G, et al. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. 2012;379(9817):713-720.
129.
Ahuja AK, Behrend MR. The Argus™ II retinal prosthesis: factors affecting patient selection for implantation. Prog Retin Eye Res. 2013;36:1-23.
Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Published: 15 March 2017
Issue date: December 2017

Copyright

© 2017 The Author(s).

Acknowledgements

Part of this work was funded by Dr. Si-Wei You’s National Program on Key Basic Research Project of China (973 Program: 2014CB542202), by Dr. Fang Kuang’s National Natural Foundation of China (81470631); and by Dr. Kwok-Fai So’s National Program on Key Basic Research Project of China (973 Programs: 2011CB707501 and 2014CB542205); Leading Talents of Guangdong (2013), the Programme of Introducing Talents of Discipline to Universities (B14036), Project of International as well as Hong Kong, Macao & Taiwan Science and Technology Cooperation Innovation Platform in Universities in Guangdong Province (2013gjhz0002), and Jinan University Guangdong-Hong Kong-Macau Cooperation and Innovation Center for Tissue Regeneration and Repair.

Rights and permissions

© 2017 You et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).

Return