1932

Abstract

The damage or loss of retinal ganglion cells (RGCs) and their axons accounts for the visual functional defects observed after traumatic injury, in degenerative diseases such as glaucoma, or in compressive optic neuropathies such as from optic glioma. By using optic nerve crush injury models, recent studies have revealed the cellular and molecular logic behind the regenerative failure of injured RGC axons in adult mammals and suggested several strategies with translational potential. This review summarizes these findings and discusses challenges for developing clinically applicable neural repair strategies.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-vision-022720-094953
2020-09-15
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/vision/6/1/annurev-vision-022720-094953.html?itemId=/content/journals/10.1146/annurev-vision-022720-094953&mimeType=html&fmt=ahah

Literature Cited

  1. Aguayo AJ, Rasminsky M, Bray GM, Carbonetto S, McKerracher L et al. 1991. Degenerative and regenerative responses of injured neurons in the central nervous system of adult mammals. Philos. Trans. R. Soc. Lond. B 331:337–43
    [Google Scholar]
  2. Anderson MA, Burda JE, Ren Y, Ao Y, O'Shea TM et al. 2016. Astrocyte scar formation aids central nervous system axon regeneration. Nature 532:195–200
    [Google Scholar]
  3. Apara A, Galvao J, Wang Y, Blackmore M, Trillo A et al. 2017. KLF9 and JNK3 interact to suppress axon regeneration in the adult CNS. J. Neurosci. 37:9632–44
    [Google Scholar]
  4. Atwal JK, Pinkston-Gosse J, Syken J, Stawicki S, Wu Y et al. 2008. PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science 322:967–70
    [Google Scholar]
  5. Baden T, Berens P, Franke K, Román Rosón M, Bethge M, Euler T 2016. The functional diversity of retinal ganglion cells in the mouse. Nature 529:345–50
    [Google Scholar]
  6. Baldwin KT, Carbajal KS, Segal BM, Giger RJ 2015. Neuroinflammation triggered by beta-glucan/dectin-1 signaling enables CNS axon regeneration. PNAS 112:2581–86
    [Google Scholar]
  7. Bei F, Lee HHC, Liu X, Gunner G, Jin H et al. 2016. Restoration of visual function by enhancing conduction in regenerated axons. Cell 164:219–32
    [Google Scholar]
  8. Belin S, Nawabi H, Wang C, Tang S, Latremoliere A et al. 2015. Injury-induced decline of intrinsic regenerative ability revealed by quantitative proteomics. Neuron 86:1000–14
    [Google Scholar]
  9. Benowitz LI, He Z, Goldberg JL 2017. Reaching the brain: advances in optic nerve regeneration. Exp. Neurol. 287:365–73
    [Google Scholar]
  10. Berry M, Carlile J, Hunter A 1996. Peripheral nerve explants grafted into the vitreous body of the eye promote the regeneration of retinal ganglion cell axons severed in the optic nerve. J. Neurocytol. 25:147–70
    [Google Scholar]
  11. Berson DM, Dunn FA, Takao M 2002. Phototransduction by retinal ganglion cells that set the circadian clock. Science 295:1070–73
    [Google Scholar]
  12. Boczek T, Cameron EG, Yu W, Xia X, Shah SH et al. 2019. Regulation of neuronal survival and axon growth by a perinuclear cAMP compartment. J. Neurosci. 39:5466–80
    [Google Scholar]
  13. Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS et al. 2002. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416:636–40
    [Google Scholar]
  14. Bray ER, Yungher BJ, Levay K, Ribeiro M, Dvoryanchikov G et al. 2019. Thrombospondin-1 mediates axon regeneration in retinal ganglion cells. Neuron 103:642–57.e7
    [Google Scholar]
  15. Bray GM, Villegas-Perez MP, Vidal-Sanz M, Carter DA, Aguayo AJ 1991. Neuronal and nonneuronal influences on retinal ganglion cell survival, axonal regrowth, and connectivity after axotomy. Ann. N. Y. Acad. Sci. 633:214–28
    [Google Scholar]
  16. Carter DA, Bray GM, Aguayo AJ 1989. Regenerated retinal ganglion cell axons can form well-differentiated synapses in the superior colliculus of adult hamsters. J. Neurosci. 9:4042–50
    [Google Scholar]
  17. Cartoni R, Norsworthy MW, Bei F, Wang C, Li S et al. 2016. The mammalian-specific protein Armcx1 regulates mitochondrial transport during axon regeneration. Neuron 92:1294–307
    [Google Scholar]
  18. Chang KC, Hertz J, Zhang X, Jin XL, Shaw P et al. 2017. Novel regulatory mechanisms for the SoxC transcriptional network required for visual pathway development. J. Neurosci. 37:4967–81
    [Google Scholar]
  19. Chen DF, Jhaveri S, Schneider GE 1995. Intrinsic changes in developing retinal neurons result in regenerative failure of their axons. PNAS 92:7287–91
    [Google Scholar]
  20. Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L et al. 2000. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403:434–39
    [Google Scholar]
  21. Chierzi S, Strettoi E, Cenni MC, Maffei L 1999. Optic nerve crush: axonal responses in wild-type and bcl-2 transgenic mice. J. Neurosci. 19:8367–76
    [Google Scholar]
  22. Clark BS, Stein-O'Brien GL, Shiau F, Cannon GH, Davis-Marcisak E et al. 2019. Single-cell RNA-seq analysis of retinal development identifies NFI factors as regulating mitotic exit and late-born cell specification. Neuron 102:1111–26.e5
    [Google Scholar]
  23. Cui Q, Yip HK, Zhao RC, So KF, Harvey AR 2003. Intraocular elevation of cyclic AMP potentiates ciliary neurotrophic factor-induced regeneration of adult rat retinal ganglion cell axons. Mol. Cell Neurosci. 22:49–61
    [Google Scholar]
  24. Daniel S, Clark AF, McDowell CM 2018. Subtype-specific response of retinal ganglion cells to optic nerve crush. Cell Death Discov 4:67
    [Google Scholar]
  25. de Lima S, Koriyama Y, Kurimoto T, Oliveira JT, Yin Y et al. 2012. Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors. PNAS 109:9149–54
    [Google Scholar]
  26. Della Santina L, Inman DM, Lupien CB, Horner PJ, Wong RO 2013. Differential progression of structural and functional alterations in distinct retinal ganglion cell types in a mouse model of glaucoma. J. Neurosci. 33:17444–57
    [Google Scholar]
  27. Dickendesher TL, Baldwin KT, Mironova YA, Koriyama Y, Raiker SJ et al. 2012. NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat. Neurosci. 15:703–12
    [Google Scholar]
  28. Domeniconi M, Cao Z, Spencer T, Sivasankaran R, Wang K et al. 2002. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron 35:283–90
    [Google Scholar]
  29. Duan X, Qiao M, Bei F, Kim IJ, He Z, Sanes JR 2015. Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signaling. Neuron 85:1244–56
    [Google Scholar]
  30. Enes J, Langwieser N, Ruschel J, Carballosa-Gonzalez MM, Klug A et al. 2010. Electrical activity suppresses axon growth through Ca(v)1.2 channels in adult primary sensory neurons. Curr. Biol. 20:1154–64
    [Google Scholar]
  31. Fischer D, He Z, Benowitz LI 2004. Counteracting the Nogo receptor enhances optic nerve regeneration if retinal ganglion cells are in an active growth state. J. Neurosci. 24:1646–51
    [Google Scholar]
  32. Fischer D, Heiduschka P, Thanos S 2001. Lens-injury-stimulated axonal regeneration throughout the optic pathway of adult rats. Exp. Neurol. 172:257–72
    [Google Scholar]
  33. Fournier AE, GrandPre T, Strittmatter SM 2001. Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature 409:341–46
    [Google Scholar]
  34. Freret ME, Gutmann DH. 2019. Insights into optic pathway glioma vision loss from mouse models of neurofibromatosis type 1. J. Neurosci. Res. 97:45–56
    [Google Scholar]
  35. Galvao J, Iwao K, Apara A, Wang Y, Ashouri M et al. 2018. The Kruppel-like factor gene target Dusp14 regulates axon growth and regeneration. Investig. Ophthalmol. Vis. Sci. 59:2736–47
    [Google Scholar]
  36. Geoffroy CG, Zheng B. 2014. Myelin-associated inhibitors in axonal growth after CNS injury. Curr. Opin. Neurobiol. 27:31–38
    [Google Scholar]
  37. Goldberg JL, Espinosa JS, Xu Y, Davidson N, Kovacs GT, Barres BA 2002a. Retinal ganglion cells do not extend axons by default: promotion by neurotrophic signaling and electrical activity. Neuron 33:689–702
    [Google Scholar]
  38. Goldberg JL, Klassen MP, Hua Y, Barres BA 2002b. Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells. Science 296:1860–64
    [Google Scholar]
  39. GrandPre T, Nakamura F, Vartanian T, Strittmatter SM 2000. Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature 403:439–44
    [Google Scholar]
  40. Hammarlund M, Nix P, Hauth L, Jorgensen EM, Bastiani M 2009. Axon regeneration requires a conserved MAP kinase pathway. Science 323:802–6
    [Google Scholar]
  41. Hattar S, Liao HW, Takao M, Berson DM, Yau KW 2002. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295:1065–70
    [Google Scholar]
  42. Irwin N, Li YM, O'Toole JE, Benowitz LI 2006. Mst3b, a purine-sensitive Ste20-like protein kinase, regulates axon outgrowth. PNAS 103:18320–25
    [Google Scholar]
  43. Jaerve A, Muller HW. 2012. Chemokines in CNS injury and repair. Cell Tissue Res 349:229–48
    [Google Scholar]
  44. Ji SL, Tang SB. 2019. Differentiation of retinal ganglion cells from induced pluripotent stem cells: a review. Int. J. Ophthalmol. 12:152–60
    [Google Scholar]
  45. Joshi Y, Soria MG, Quadrato G, Inak G, Zhou L et al. 2015. The MDM4/MDM2-p53-IGF1 axis controls axonal regeneration, sprouting and functional recovery after CNS injury. Brain 138:1843–62
    [Google Scholar]
  46. Keirstead SA, Rasminsky M, Fukuda Y, Carter DA, Aguayo AJ, Vidal-Sanz M 1989. Electrophysiologic responses in hamster superior colliculus evoked by regenerating retinal axons. Science 246:255–57
    [Google Scholar]
  47. Kerrigan-Baumrind LA, Quigley HA, Pease ME, Kerrigan DF, Mitchell RS 2000. Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. Investig. Ophthalmol. Vis. Sci. 41:741–48
    [Google Scholar]
  48. Kondo S, Takahashi K, Kinoshita Y, Nagai J, Wakatsuki S et al. 2019. Genetic inhibition of CRMP2 phosphorylation at serine 522 promotes axonal regeneration after optic nerve injury. Sci. Rep. 9:7188
    [Google Scholar]
  49. Kottis V, Thibault P, Mikol D, Xiao ZC, Zhang R et al. 2002. Oligodendrocyte-myelin glycoprotein (OMgp) is an inhibitor of neurite outgrowth. J. Neurochem. 82:1566–69
    [Google Scholar]
  50. Kunzevitzky NJ, Almeida MV, Duan Y, Li S, Xiang M, Goldberg JL 2011. Foxn4 is required for retinal ganglion cell distal axon patterning. Mol. Cell Neurosci. 46:731–41
    [Google Scholar]
  51. Kurimoto T, Yin Y, Habboub G, Gilbert HY, Li Y et al. 2013. Neutrophils express oncomodulin and promote optic nerve regeneration. J. Neurosci. 33:14816–24
    [Google Scholar]
  52. Kurimoto T, Yin Y, Omura K, Gilbert HY, Kim D et al. 2010. Long-distance axon regeneration in the mature optic nerve: contributions of oncomodulin, cAMP, and pten gene deletion. J. Neurosci. 30:15654–63
    [Google Scholar]
  53. Kuwajima T, Soares CA, Sitko AA, Lefebvre V, Mason C 2017. SoxC transcription factors promote contralateral retinal ganglion cell differentiation and axon guidance in the mouse visual system. Neuron 93:1110–25.e5
    [Google Scholar]
  54. Leaver SG, Cui Q, Plant GW, Arulpragasam A, Hisheh S et al. 2006. AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells. Gene Ther 13:1328–41
    [Google Scholar]
  55. Leibinger M, Andreadaki A, Gobrecht P, Levin E, Diekmann H, Fischer D 2016. Boosting central nervous system axon regeneration by circumventing limitations of natural cytokine signaling. Mol. Ther. 24:1712–25
    [Google Scholar]
  56. Leibinger M, Muller A, Andreadaki A, Hauk TG, Kirsch M, Fischer D 2009. 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. 29:14334–41
    [Google Scholar]
  57. Leon S, Yin Y, Nguyen J, Irwin N, Benowitz LI 2000. Lens injury stimulates axon regeneration in the mature rat optic nerve. J. Neurosci. 20:4615–26
    [Google Scholar]
  58. Li S, He Q, Wang H, Tang X, Ho KW et al. 2015. Injured adult retinal axons with Pten and Socs3 co-deletion reform active synapses with suprachiasmatic neurons. Neurobiol. Dis. 73:366–76
    [Google Scholar]
  59. Li S, Yang C, Zhang L, Gao X, Wang X et al. 2016. Promoting axon regeneration in the adult CNS by modulation of the melanopsin/GPCR signaling. PNAS 113:1937–42
    [Google Scholar]
  60. Li Y, Andereggen L, Yuki K, Omura K, Yin Y et al. 2017. Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration. PNAS 114:E209–18
    [Google Scholar]
  61. Lim JH, Stafford BK, Nguyen PL, Lien BV, Wang C et al. 2016. Neural activity promotes long-distance, target-specific regeneration of adult retinal axons. Nat. Neurosci. 19:1073–84
    [Google Scholar]
  62. Lingor P, Tonges L, Pieper N, Bermel C, Barski E et al. 2008. ROCK inhibition and CNTF interact on intrinsic signalling pathways and differentially regulate survival and regeneration in retinal ganglion cells. Brain 131:250–63
    [Google Scholar]
  63. Lorber B, Howe ML, Benowitz LI, Irwin N 2009. Mst3b, an Ste20-like kinase, regulates axon regeneration in mature CNS and PNS pathways. Nat. Neurosci. 12:1407–14
    [Google Scholar]
  64. Mansour-Robaey S, Clarke DB, Wang YC, Bray GM, Aguayo AJ 1994. Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. PNAS 91:1632–36
    [Google Scholar]
  65. McKerracher L, David S, Jackson DL, Kottis V, Dunn RJ, Braun PE 1994. Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron 13:805–11
    [Google Scholar]
  66. Meyer-Franke A, Kaplan MR, Pfrieger FW, Barres BA 1995. Characterization of the signaling interactions that promote the survival and growth of developing retinal ganglion cells in culture. Neuron 15:805–19
    [Google Scholar]
  67. Miao L, Yang L, Huang H, Liang F, Ling C, Hu Y 2016. mTORC1 is necessary but mTORC2 and GSK3beta are inhibitory for AKT3-induced axon regeneration in the central nervous system. eLife 5:e14908
    [Google Scholar]
  68. Monsul NT, Geisendorfer AR, Han PJ, Banik R, Pease ME et al. 2004. Intraocular injection of dibutyryl cyclic AMP promotes axon regeneration in rat optic nerve. Exp. Neurol. 186:124–33
    [Google Scholar]
  69. Moore DL, Blackmore MG, Hu Y, Kaestner KH, Bixby JL et al. 2009. KLF family members regulate intrinsic axon regeneration ability. Science 326:298–301
    [Google Scholar]
  70. Mukhopadhyay G, Doherty P, Walsh FS, Crocker PR, Filbin MT 1994. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron 13:757–67
    [Google Scholar]
  71. Muller A, Hauk TG, Fischer D 2007. Astrocyte-derived CNTF switches mature RGCs to a regenerative state following inflammatory stimulation. Brain 130:3308–20
    [Google Scholar]
  72. Nakagawa S, Takada S, Takada R, Takeichi M 2003. Identification of the laminar-inducing factor: Wnt-signal from the anterior rim induces correct laminar formation of the neural retina in vitro. Dev. Biol. 260:414–25
    [Google Scholar]
  73. Nawabi H, Belin S, Cartoni R, Williams PR, Wang C et al. 2015. Doublecortin-like kinases promote neuronal survival and induce growth cone reformation via distinct mechanisms. Neuron 88:704–19
    [Google Scholar]
  74. Norsworthy MW, Bei F, Kawaguchi R, Wang Q, Tran NM et al. 2017. Sox11 expression promotes regeneration of some retinal ganglion cell types but kills others. Neuron 94:1112–20.e4
    [Google Scholar]
  75. O'Donovan KJ, Ma K, Guo H, Wang C, Sun F et al. 2014. B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS. J. Exp. Med. 211:801–14
    [Google Scholar]
  76. Pacal M, Bremner R. 2012. Mapping differentiation kinetics in the mouse retina reveals an extensive period of cell cycle protein expression in post-mitotic newborn neurons. Dev. Dyn. 241:1525–44
    [Google Scholar]
  77. Park H, Poo MM. 2013. Neurotrophin regulation of neural circuit development and function. Nat. Rev. Neurosci. 14:7–23
    [Google Scholar]
  78. Park KK, Liu K, Hu Y, Smith PD, Wang C et al. 2008. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 322:963–66
    [Google Scholar]
  79. Patel AK, Park KK, Hackam AS 2017. Wnt signaling promotes axonal regeneration following optic nerve injury in the mouse. Neuroscience 343:372–83
    [Google Scholar]
  80. Pearson CS, Mencio CP, Barber AC, Martin KR, Geller HM 2018. Identification of a critical sulfation in chondroitin that inhibits axonal regeneration. eLife 7:e37139
    [Google Scholar]
  81. Pelzel HR, Schlamp CL, Nickells RW 2010. Histone H4 deacetylation plays a critical role in early gene silencing during neuronal apoptosis. BMC Neurosci 11:62
    [Google Scholar]
  82. Pernet V, Joly S, Jordi N, Dalkara D, Guzik-Kornacka A et al. 2013. Misguidance and modulation of axonal regeneration by Stat3 and Rho/ROCK signaling in the transparent optic nerve. Cell Death Dis 4:e734
    [Google Scholar]
  83. Prinjha R, Moore SE, Vinson M, Blake S, Morrow R et al. 2000. Inhibitor of neurite outgrowth in humans. Nature 403:383–84
    [Google Scholar]
  84. Qin S, Zou Y, Zhang CL 2013. Cross-talk between KLF4 and STAT3 regulates axon regeneration. Nat. Commun. 4:2633
    [Google Scholar]
  85. Quigley HA. 2016. Understanding glaucomatous optic neuropathy: the synergy between clinical observation and investigation. Annu. Rev. Vis. Sci. 2:235–54
    [Google Scholar]
  86. Rheaume BA, Jereen A, Bolisetty M, Sajid MS, Yang Y et al. 2018. Single cell transcriptome profiling of retinal ganglion cells identifies cellular subtypes. Nat. Commun. 9:2759
    [Google Scholar]
  87. Robinson GA, Madison RD. 2004. Axotomized mouse retinal ganglion cells containing melanopsin show enhanced survival, but not enhanced axon regrowth into a peripheral nerve graft. Vis. Res. 44:2667–74
    [Google Scholar]
  88. Sanes JR, Masland RH. 2015. The types of retinal ganglion cells: current status and implications for neuronal classification. Annu. Rev. Neurosci. 38:221–46
    [Google Scholar]
  89. Sapieha PS, Peltier M, Rendahl KG, Manning WC, Di Polo A 2003. Fibroblast growth factor-2 gene delivery stimulates axon growth by adult retinal ganglion cells after acute optic nerve injury. Mol. Cell Neurosci. 24:656–72
    [Google Scholar]
  90. Schiapparelli LM, Shah SH, Ma Y, McClatchy DB, Sharma P et al. 2019. The retinal ganglion cell transportome identifies proteins transported to axons and presynaptic compartments in the visual system in vivo. Cell Rep 28:1935–47.e5
    [Google Scholar]
  91. Schmitt HM, Schlamp CL, Nickells RW 2016. Role of HDACs in optic nerve damage-induced nuclear atrophy of retinal ganglion cells. Neurosci. Lett. 625:11–15
    [Google Scholar]
  92. Segal RA, Greenberg ME. 1996. Intracellular signaling pathways activated by neurotrophic factors. Annu. Rev. Neurosci. 19:463–89
    [Google Scholar]
  93. Shah SH, Goldberg JL. 2018. The role of axon transport in neuroprotection and regeneration. Dev. Neurobiol. 78:998–1010
    [Google Scholar]
  94. Shaw PX, Sang A, Wang Y, Ho D, Douglas C et al. 2017. Topical administration of a Rock/Net inhibitor promotes retinal ganglion cell survival and axon regeneration after optic nerve injury. Exp. Eye Res. 158:33–42
    [Google Scholar]
  95. Smith PD, Sun F, Park KK, Cai B, Wang C et al. 2009. SOCS3 deletion promotes optic nerve regeneration in vivo. Neuron 64:617–23
    [Google Scholar]
  96. So KF, Schneider GE, Ayres S 1981. Lesions of the brachium of the superior colliculus in neonate hamsters: correlation of anatomy with behavior. Exp. Neurol. 72:379–400
    [Google Scholar]
  97. Sun F, Park KK, Belin S, Wang D, Lu T et al. 2011. Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature 480:372–75
    [Google Scholar]
  98. Tedeschi A, Dupraz S, Laskowski CJ, Xue J, Ulas T et al. 2016. The calcium channel subunit Alpha2delta2 suppresses axon regeneration in the adult CNS. Neuron 92:419–34
    [Google Scholar]
  99. Trakhtenberg EF, Li Y, Feng Q, Tso J, Rosenberg PA et al. 2018. Zinc chelation and Klf9 knockdown cooperatively promote axon regeneration after optic nerve injury. Exp. Neurol. 300:22–29
    [Google Scholar]
  100. Tran NM, Shekhar K, Whitney IE, Jacobi A, Benhar I et al. 2019. Single-cell profiles of retinal ganglion cells differing in resilience to injury reveal neuroprotective genes. Neuron 104:1039–55.e12
    [Google Scholar]
  101. Venugopalan P, Wang Y, Nguyen T, Huang A, Muller KJ, Goldberg JL 2016. Transplanted neurons integrate into adult retinas and respond to light. Nat. Commun. 7:10472
    [Google Scholar]
  102. Vidal-Sanz M, Bray GM, Villegas-Perez MP, Thanos S, Aguayo AJ 1987. Axonal regeneration and synapse formation in the superior colliculus by retinal ganglion cells in the adult rat. J. Neurosci. 7:2894–909
    [Google Scholar]
  103. Villegas-Perez MP, Vidal-Sanz M, Bray GM, Aguayo AJ 1988. Influences of peripheral nerve grafts on the survival and regrowth of axotomized retinal ganglion cells in adult rats. J. Neurosci. 8:265–80
    [Google Scholar]
  104. Wang KC, Kim JA, Sivasankaran R, Segal R, He Z 2002. P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature 420:74–78
    [Google Scholar]
  105. Wang X, Lin J, Arzeno A, Choi JY, Boccio J et al. 2015a. Intravitreal delivery of human NgR-Fc decoy protein regenerates axons after optic nerve crush and protects ganglion cells in glaucoma models. Investig. Ophthalmol. Vis. Sci. 56:1357–66
    [Google Scholar]
  106. Wang XW, Li Q, Liu CM, Hall PA, Jiang JJ et al. 2018. Lin28 signaling supports mammalian PNS and CNS axon regeneration. Cell Rep 24:2540–52.e6
    [Google Scholar]
  107. Wang Y, Cameron EG, Li J, Stiles TL, Kritzer MD et al. 2015b. Muscle A-kinase anchoring protein-alpha is an injury-specific signaling scaffold required for neurotrophic- and cyclic adenosine monophosphate-mediated survival. EBioMedicine 2:1880–87
    [Google Scholar]
  108. Watkins TA, Wang B, Huntwork-Rodriguez S, Yang J, Jiang Z et al. 2013. DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury. PNAS 110:4039–44
    [Google Scholar]
  109. Weng YL, An R, Cassin J, Joseph J, Mi R et al. 2017. An intrinsic epigenetic barrier for functional axon regeneration. Neuron 94:337–46.e6
    [Google Scholar]
  110. Weng YL, Wang X, An R, Cassin J, Vissers C et al. 2018. Epitranscriptomic m(6)A regulation of axon regeneration in the adult mammalian nervous system. Neuron 97:313–25.e6
    [Google Scholar]
  111. Xie L, Yin Y, Gilbert H-Y, Benowitz LI 2019. Effects of CNTF gene therapy on optic nerve regeneration and RGC survival involve neuroinflammation and other growth factors. 2019 Proceedings of Neuroscience 2019, Oct. 19–23, Chicago Art. 188.09 Washington, DC: Soc. Neurosci.
    [Google Scholar]
  112. Yang L, Miao L, Liang F, Huang H, Teng X et al. 2014. The mTORC1 effectors S6K1 and 4E-BP play different roles in CNS axon regeneration. Nat. Commun. 5:5416
    [Google Scholar]
  113. Yin Y, Cui Q, Gilbert HY, Yang Y, Yang Z et al. 2009. Oncomodulin links inflammation to optic nerve regeneration. PNAS 106:19587–92
    [Google Scholar]
  114. Yin Y, Cui Q, Li Y, Irwin N, Fischer D et al. 2003. Macrophage-derived factors stimulate optic nerve regeneration. J. Neurosci. 23:2284–93
    [Google Scholar]
  115. Yin Y, Henzl MT, Lorber B, Nakazawa T, Thomas TT et al. 2006. Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nat. Neurosci. 9:843–52
    [Google Scholar]
  116. Yin Y, Xie L, Gilbert H-Y, Cen LP, Li Y et al. 2018. SDF1 is highly expressed in macrophages and contributes to inflammation-induced optic nerve regeneration. Proceedings of Neuroscience 2018, Nov. 3–7, San Diego Art. 115.18 Washington, DC: Soc. Neurosci.
    [Google Scholar]
  117. You SW, Hellstrom M, Pollett MA, LeVaillant C, Moses C et al. 2016. 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. 279:197–211
    [Google Scholar]
  118. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL et al. 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–20
    [Google Scholar]
  119. Zhang Y, Williams PR, Jacobi A, Wang C, Goel A et al. 2019. Elevating growth factor responsiveness and axon regeneration by modulating presynaptic inputs. Neuron 103:39–51.e5
    [Google Scholar]
/content/journals/10.1146/annurev-vision-022720-094953
Loading
/content/journals/10.1146/annurev-vision-022720-094953
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error