Molecular Neurobiology

, Volume 42, Issue 3, pp 199–209 | Cite as

Turning Müller Glia into Neural Progenitors in the Retina

Article

Abstract

Stimulating neuronal regeneration is a potential strategy to treat sight-threatening diseases of the retina. In some classes of vertebrates, retinal regeneration occurs spontaneously to effectively replace neurons lost to acute damage in order to restore visual function. There are different mechanisms and cellular sources of retinal regeneration in different species, include the retinal pigmented epithelium, progenitors seeded across the retina, and the Müller glia. This review briefly summarizes the different mechanisms of retinal regeneration in frogs, fish, chicks, and rodents. The bulk of this review summarizes and discusses recent findings regarding regeneration from Müller glia-derived progenitors, with emphasis on findings in the chick retina. The Müller glia are a promising source of regeneration-supporting cells that are intrinsic to the retina and significant evidence indicated these glias can be stimulated to produce neurons in different classes of vertebrates. The key to harnessing the neurogenic potential of Müller glia is to identify the secreted factors, signaling pathways, and transcription factors that enable de-differentiation, proliferation, and neurogenesis. We review findings regarding the roles of mitogen-activated protein kinase and notch signaling in the proliferation and generation of Müller glia-derived retinal progenitors.

Keywords

Retina Müller glia Neuronal progenitors 

References

  1. 1.
    Stone L (1950) Neural retina degeneration followed by regeneration from surviving pigment cells in grafted adult salamander eyes. Anat Rec 106:89–110CrossRefPubMedGoogle Scholar
  2. 2.
    Stone L (1950) The role of retinal pigment cells in regenerating neural retinae of adult salamander eyes. J Exp Zool 113:9–31CrossRefGoogle Scholar
  3. 3.
    Akimenko MA, Mari-Beffa M, Becerra J, Geraudie J (2003) Old questions, new tools, and some answers to the mystery of fin regeneration. Dev Dyn 226:190–201CrossRefPubMedGoogle Scholar
  4. 4.
    Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in zebrafish. Science 298:2188–2190CrossRefPubMedGoogle Scholar
  5. 5.
    Becker CG, Becker T (2008) Adult zebrafish as a model for successful central nervous system regeneration. Restor Neurol Neurosci 26:71–80PubMedGoogle Scholar
  6. 6.
    Bernhardt RR, Tongiorgi E, Anzini P, Schachner M (1996) Increased expression of specific recognition molecules by retinal ganglion cells and by optic pathway glia accompanies the successful regeneration of retinal axons in adult zebrafish. J Comp Neurol 376:253–264CrossRefPubMedGoogle Scholar
  7. 7.
    Vihtelic TS, Hyde DR (2000) Light-induced rod and cone cell death and regeneration in the adult albino zebrafish (Danio rerio) retina. J Neurobiol 44:289–307CrossRefPubMedGoogle Scholar
  8. 8.
    Hitchcock P, Ochocinska M, Sieh A, Otteson D (2004) Persistent and injury-induced neurogenesis in the vertebrate retina. Prog Retin Eye Res 23:183–194CrossRefPubMedGoogle Scholar
  9. 9.
    Hitchcock PF, Raymond PA (1992) Retinal regeneration. Trends Neurosci 15:103–108CrossRefPubMedGoogle Scholar
  10. 10.
    Raymond PA, Hitchcock PF (2000) How the neural retina regenerates. Results Probl Cell Differ 31:197–218PubMedGoogle Scholar
  11. 11.
    Montgomery JE, Parsons MJ, Hyde DR (2010) A novel model of retinal ablation demonstrates that the extent of rod cell death regulates the origin of the regenerated zebrafish rod photoreceptors. J Comp Neurol 518:800–14CrossRefPubMedGoogle Scholar
  12. 12.
    Bernardos RL, Barthel LK, Meyers JR, Raymond PA (2007) Late-stage neuronal progenitors in the retina are radial Muller glia that function as retinal stem cells. J Neurosci 27:7028–7040CrossRefPubMedGoogle Scholar
  13. 13.
    Fausett BV, Goldman D (2006) A role for alpha1 tubulin-expressing Muller glia in regeneration of the injured zebrafish retina. J Neurosci 26:6303–6313CrossRefPubMedGoogle Scholar
  14. 14.
    Qin Z, Barthel LK, Raymond PA (2009) Genetic evidence for shared mechanisms of epimorphic regeneration in zebrafish. Proc Natl Acad Sci USA 106:9310–9315CrossRefPubMedGoogle Scholar
  15. 15.
    Stenkamp DL, Powers MK, Carney LH, Cameron DA (2001) Evidence for two distinct mechanisms of neurogenesis and cellular pattern formation in regenerated goldfish retinas. J Comp Neurol 431:363–381CrossRefPubMedGoogle Scholar
  16. 16.
    Becker CG, Becker T (2007) Growth and pathfinding of regenerating axons in the optic projection of adult fish. J Neurosci Res 85:2793–2799CrossRefPubMedGoogle Scholar
  17. 17.
    Stenkamp DL (2007) Neurogenesis in the fish retina. Int Rev Cytol 259:173–224CrossRefPubMedGoogle Scholar
  18. 18.
    Yokoyama H (2008) Initiation of limb regeneration: the critical steps for regenerative capacity. Dev Growth Differ 50:13–22CrossRefPubMedGoogle Scholar
  19. 19.
    Kurosaka H, Takano-Yamamoto T, Yamashiro T, Agata K (2008) Comparison of molecular and cellular events during lower jaw regeneration of newt (Cynops pyrrhogaster) and West African clawed frog (Xenopus tropicalis). Dev Dyn 237:354–365CrossRefPubMedGoogle Scholar
  20. 20.
    Singh BN, Koyano-Nakagawa N, Garry JP, Weaver CV (2010) Heart of newt: a recipe for regeneration. J Cardiovasc Transl Res 3:397–409CrossRefPubMedGoogle Scholar
  21. 21.
    Mitsuda S, Yoshii C, Ikegami Y, Araki M (2005) Tissue interaction between the retinal pigment epithelium and the choroid triggers retinal regeneration of the newt Cynops pyrrhogaster. Dev Biol 280:122–132CrossRefPubMedGoogle Scholar
  22. 22.
    Mizuno N, Mochii M, Yamamoto TS, Takahashi TC, Eguchi G, Okada TS (1999) Pax-6 and Prox 1 expression during lens regeneration from Cynops iris and Xenopus cornea: evidence for a genetic program common to embryonic lens development. Differentiation 65:141–149CrossRefPubMedGoogle Scholar
  23. 23.
    Margotta V, Filoni S, Merante A, Chimenti C (2002) Analysis of morphogenetic potential of caudal spinal cord in Triturus carnifex adults (Urodele amphibians) subjected to repeated tail amputations. Ital J Anat Embryol 107:127–144PubMedGoogle Scholar
  24. 24.
    Stroeva OG, Mitashov VI (1983) Retinal pigment epithelium: proliferation and differentiation during development and regeneration. Int Rev Cytol 83:221–293CrossRefPubMedGoogle Scholar
  25. 25.
    Okada TS (1980) Cellular metaplasia or transdifferentiation as a model for retinal cell differentiation. Curr Top Dev Biol 16:349–380CrossRefPubMedGoogle Scholar
  26. 26.
    Negishi K, Shinagawa S (1993) Fibroblast growth factor induces proliferating cell nuclear antigen-immunoreactive cells in goldfish retina. Neurosci Res 18:143–56Google Scholar
  27. 27.
    Reh TA (1987) Cell-specific regulation of neuronal production in the larval frog retina. J Neurosci 7:3317–3324PubMedGoogle Scholar
  28. 28.
    Reh TA, Nagy T, Gretton H (1987) Retinal pigmented epithelial cells induced to transdifferentiate to neurons by laminin. Nature 330:68–71CrossRefPubMedGoogle Scholar
  29. 29.
    Araki M (2007) Regeneration of the amphibian retina: role of tissue interaction and related signaling molecules on RPE transdifferentiation. Dev Growth Differ 49:109–120CrossRefPubMedGoogle Scholar
  30. 30.
    Reh TA, Jones M, Pittack C (1991) Common mechanisms of retinal regeneration in the larval frog and embryonic chick. Ciba Found Symp 160:192–204, discussion 204–8PubMedGoogle Scholar
  31. 31.
    Sakaguchi DS, Janick LM, Reh TA (1997) Basic fibroblast growth factor (FGF-2) induced transdifferentiation of retinal pigment epithelium: generation of retinal neurons and glia. Dev Dyn 209:387–398CrossRefPubMedGoogle Scholar
  32. 32.
    Park CM, Hollenberg MJ (1989) Basic fibroblast growth factor induces retinal regeneration in vivo. Dev Biol 134:201–205CrossRefPubMedGoogle Scholar
  33. 33.
    Park CM, Hollenberg MJ (1991) Induction of retinal regeneration in vivo by growth factors. Dev Biol 148:322–333CrossRefPubMedGoogle Scholar
  34. 34.
    Pittack C, Jones M, Reh TA (1991) Basic fibroblast growth factor induces retinal pigment epithelium to generate neural retina in vitro. Development 113:577–588PubMedGoogle Scholar
  35. 35.
    Zhao S, Thornquist SC, Barnstable CJ (1995) In vitro transdifferentiation of embryonic rat retinal pigment epithelium to neural retina. Brain Res 677:300–310CrossRefPubMedGoogle Scholar
  36. 36.
    Coulombre JL, Coulombre AJ (1965) Regeneration of neural retina from the pigmented epithelium in the chick embryo. Dev Biol 12:79–92CrossRefPubMedGoogle Scholar
  37. 37.
    Park CM, Hollenberg MJ (1993) Growth factor-induced retinal regeneration in vivo. Int Rev Cytol 146:49–74CrossRefPubMedGoogle Scholar
  38. 38.
    Vogel-Hopker A, Momose T, Rohrer H, Yasuda K, Ishihara L, Rapaport DH (2000) Multiple functions of fibroblast growth factor-8 (FGF-8) in chick eye development. Mech Dev 94:25–36CrossRefPubMedGoogle Scholar
  39. 39.
    Haynes T, Gutierrez C, Aycinena JC, Tsonis PA, Del Rio-Tsonis K (2007) BMP signaling mediates stem/progenitor cell-induced retina regeneration. Proc Natl Acad Sci USA 104:20380–20385PubMedGoogle Scholar
  40. 40.
    Spence JR, Aycinena JC, Del Rio-Tsonis K (2007) Fibroblast growth factor-hedgehog interdependence during retina regeneration. Dev Dyn 236:1161–1174CrossRefPubMedGoogle Scholar
  41. 41.
    Spence JR, Madhavan M, Ewing JD, Jones DK, Lehman BM, Del Rio-Tsonis K (2004) The hedgehog pathway is a modulator of retina regeneration. Development 131:4607–4621CrossRefPubMedGoogle Scholar
  42. 42.
    Wang SZ, Ma W, Yan RT, Mao W (2010) Generating retinal neurons by reprogramming retinal pigment epithelial cells. Expert Opin Biol Ther 10:1227–1239CrossRefPubMedGoogle Scholar
  43. 43.
    Fischer AJ, Reh TA (2001) Transdifferentiation of pigmented epithelial cells: a source of retinal stem cells? Dev Neurosci 23:268–276CrossRefPubMedGoogle Scholar
  44. 44.
    Fischer AJ, Reh TA (2000) Identification of a proliferating marginal zone of retinal progenitors in postnatal chickens. Dev Biol 220:197–210CrossRefPubMedGoogle Scholar
  45. 45.
    Kubota R, Hokoc JN, Moshiri A, McGuire C, Reh TA (2002) A comparative study of neurogenesis in the retinal ciliary marginal zone of homeothermic vertebrates. Brain Res Dev Brain Res 134:31–41CrossRefPubMedGoogle Scholar
  46. 46.
    Fischer AJ (2005) Neural regeneration in the chick retina. Prog Retin Eye Res 24:161–182CrossRefPubMedGoogle Scholar
  47. 47.
    Fischer AJ, Reh TA (2003) Growth factors induce neurogenesis in the ciliary body. Dev Biol 259:225–240CrossRefPubMedGoogle Scholar
  48. 48.
    Tropepe V, Coles BL, Chiasson BJ, Horsford DJ, Elia AJ, McInnes RR, van der Kooy D (2000) Retinal stem cells in the adult mammalian eye. Science 287:2032–2036CrossRefPubMedGoogle Scholar
  49. 49.
    Cicero SA, Johnson D, Reyntjens S, Frase S, Connell S, Chow LM, Baker SJ, Sorrentino BP, Dyer MA (2009) Cells previously identified as retinal stem cells are pigmented ciliary epithelial cells. Proc Natl Acad Sci USA 106:6685–6690CrossRefPubMedGoogle Scholar
  50. 50.
    Gualdoni S, Baron M, Lakowski J, Decembrini S, Smith AJ, Pearson RA, Ali RR, Sowden JC (2010) Adult ciliary epithelial cells, previously identified as retinal stem cells with potential for retinal repair, fail to differentiate into new rod photoreceptors. Stem Cells 28:1048–1059CrossRefPubMedGoogle Scholar
  51. 51.
    Moshiri A, Reh TA (2004) Persistent progenitors at the retinal margin of ptc+/−mice. J Neurosci 24:229–237CrossRefPubMedGoogle Scholar
  52. 52.
    Fischer AJ, Scott MA, Zelinka C, Sherwood P (2010) A novel type of glial cell in the retina is stimulated by insulin-like growth factor 1 and may exacerbate damage to neurons and Muller glia. Glia 58:633–649PubMedCrossRefGoogle Scholar
  53. 53.
    Rompani SB, Cepko CL (2010) A common progenitor for retinal astrocytes and oligodendrocytes. J Neurosci 30:4970–4980CrossRefPubMedGoogle Scholar
  54. 54.
    Fischer AJ, Reh TA (2001) Muller glia are a potential source of neural regeneration in the postnatal chicken retina. Nat Neurosci 4:247–252CrossRefPubMedGoogle Scholar
  55. 55.
    Karl MO, Hayes S, Nelson BR, Tan K, Buckingham B, Reh TA (2008) Stimulation of neural regeneration in the mouse retina. Proc Natl Acad Sci USA 105:19508–19513CrossRefPubMedGoogle Scholar
  56. 56.
    Ooto S, Akagi T, Kageyama R, Akita J, Mandai M, Honda Y, Takahashi M (2004) Potential for neural regeneration after neurotoxic injury in the adult mammalian retina. Proc Natl Acad Sci USA 101:13654–13659CrossRefPubMedGoogle Scholar
  57. 57.
    Fischer AJ, McGuire CR, Dierks BD, Reh TA (2002) Insulin and fibroblast growth factor 2 activate a neurogenic program in Muller glia of the chicken retina. J Neurosci 22:9387–9398PubMedGoogle Scholar
  58. 58.
    Fischer AJ, Scott MA, Tuten W (2009) Mitogen-activated protein kinase-signaling stimulates Muller glia to proliferate in acutely damaged chicken retina. Glia 57:166–181CrossRefPubMedGoogle Scholar
  59. 59.
    Hayes S, Nelson BR, Buckingham B, Reh TA (2007) Notch signaling regulates regeneration in the avian retina. Dev Biol 312:300–311CrossRefPubMedGoogle Scholar
  60. 60.
    Fischer AJ, Scott MA, Ritchey ER, Sherwood P (2009) Mitogen-activated protein kinase-signaling regulates the ability of Muller glia to proliferate and protect retinal neurons against excitotoxicity. Glia 57:1538–1552CrossRefPubMedGoogle Scholar
  61. 61.
    Thummel R, Enright JM, Kassen SC, Montgomery JE, Bailey TJ, Hyde DR (2010) Pax6a and Pax6b are required at different points in neuronal progenitor cell proliferation during zebrafish photoreceptor regeneration. Exp Eye Res 90:572–582CrossRefPubMedGoogle Scholar
  62. 62.
    Fausett BV, Gumerson JD, Goldman D (2008) The proneural basic helix-loop-helix gene ascl1a is required for retina regeneration. J Neurosci 28:1109–1117CrossRefPubMedGoogle Scholar
  63. 63.
    Bernardos RL, Lentz SI, Wolfe MS, Raymond PA (2005) Notch-Delta signaling is required for spatial patterning and Muller glia differentiation in the zebrafish retina. Dev Biol 278:381–395CrossRefPubMedGoogle Scholar
  64. 64.
    Raymond PA, Barthel LK, Bernardos RL, Perkowski JJ (2006) Molecular characterization of retinal stem cells and their niches in adult zebrafish. BMC Dev Biol 6:36CrossRefPubMedGoogle Scholar
  65. 65.
    Fischer AJ, Omar G (2005) Transitin, a nestin-related intermediate filament, is expressed by neural progenitors and can be induced in Muller glia in the chicken retina. J Comp Neurol 484:1–14CrossRefPubMedGoogle Scholar
  66. 66.
    Reh TA, Fischer AJ (2001) Stem cells in the vertebrate retina. Brain Behav Evol 58:296–305CrossRefPubMedGoogle Scholar
  67. 67.
    Fischer AJ, Reh TA (2003) Potential of Muller glia to become neurogenic retinal progenitor cells. Glia 43:70–76CrossRefPubMedGoogle Scholar
  68. 68.
    Yurco P, Cameron DA (2005) Responses of Muller glia to retinal injury in adult zebrafish. Vis Res 45:991–1002CrossRefPubMedGoogle Scholar
  69. 69.
    Lawrence JM, Singhal S, Bhatia B, Keegan DJ, Reh TA, Luthert PJ, Khaw PT, Limb GA (2007) MIO-M1 cells and similar muller glial cell lines derived from adult human retina exhibit neural stem cell characteristics. Stem Cells 25:2033–2043CrossRefPubMedGoogle Scholar
  70. 70.
    Fischer AJ, Wang SZ, Reh TA (2004) NeuroD induces the expression of visinin and calretinin by proliferating cells derived from toxin-damaged chicken retina. Dev Dyn 229:555–563CrossRefPubMedGoogle Scholar
  71. 71.
    Fischer AJ, Schmidt M, Omar G, Reh TA (2004) BMP4 and CNTF are neuroprotective and suppress damage-induced proliferation of Muller glia in the retina. Mol Cell Neurosci 27:531–542CrossRefPubMedGoogle Scholar
  72. 72.
    Stuermer CA, Easter SS, Jr (1984) A comparison of the normal and regenerated retinotectal pathways of goldfish. J Comp Neurol 223:57–76Google Scholar
  73. 73.
    Hitchcock PF, Cirenza P (1994) Synaptic organization of regenerated retina in the goldfish. J Comp Neurol 343:609–616Google Scholar
  74. 74.
    Fimbel SM, Montgomery JE, Burket CT, Hyde DR (2007) Regeneration of inner retinal neurons after intravitreal injection of ouabain in zebrafish. J Neurosci 27:1712–1724CrossRefPubMedGoogle Scholar
  75. 75.
    Lindsey AE, Powers MK (2007) Visual behavior of adult goldfish with regenerating retina. Vis Neurosci 24:247–255CrossRefPubMedGoogle Scholar
  76. 76.
    Mensinger AF, Powers MK (1999) Visual function in regenerating teleost retina following cytotoxic lesioning. Vis Neurosci 16:241–251CrossRefPubMedGoogle Scholar
  77. 77.
    Mensinger AF, Powers MK (2007) Visual function in regenerating teleost retina following surgical lesioning. Vis Neurosci 24:299–307CrossRefPubMedGoogle Scholar
  78. 78.
    Sherpa T, Fimbel SM, Mallory DE, Maaswinkel H, Spritzer SD, Sand JA, Li L, Hyde DR, Stenkamp DL (2008) Ganglion cell regeneration following whole-retina destruction in zebrafish. Dev Neurobiol 68:166–181CrossRefPubMedGoogle Scholar
  79. 79.
    Morris AC, Scholz TL, Brockerhoff SE, Fadool JM (2008) Genetic dissection reveals two separate pathways for rod and cone regeneration in the teleost retina. Dev Neurobiol 68:605–619CrossRefPubMedGoogle Scholar
  80. 80.
    Kassen SC, Thummel R, Campochiaro LA, Harding MJ, Bennett NA, Hyde DR (2009) CNTF induces photoreceptor neuroprotection and Muller glial cell proliferation through two different signaling pathways in the adult zebrafish retina. Exp Eye Res 88:1051–1064CrossRefPubMedGoogle Scholar
  81. 81.
    Kirsch M, Lee MY, Meyer V, Wiese A, Hofmann HD (1997) Evidence for multiple, local functions of ciliary neurotrophic factor (CNTF) in retinal development: expression of CNTF and its receptors and in vitro effects on target cells. J Neurochem 68:979–990CrossRefPubMedGoogle Scholar
  82. 82.
    Peterson WM, Wang Q, Tzekova R, Wiegand SJ (2000) Ciliary neurotrophic factor and stress stimuli activate the Jak-STAT pathway in retinal neurons and glia. J Neurosci 20:4081–4090PubMedGoogle Scholar
  83. 83.
    Wahlin KJ, Campochiaro PA, Zack DJ, Adler R (2000) Neurotrophic factors cause activation of intracellular signaling pathways in Muller cells and other cells of the inner retina, but not photoreceptors. Invest Ophthalmol Vis Sci 41:927–936PubMedGoogle Scholar
  84. 84.
    Wang Y, Smith SB, Ogilvie JM, McCool DJ, Sarthy V (2002) Ciliary neurotrophic factor induces glial fibrillary acidic protein in retinal Muller cells through the JAK/STAT signal transduction pathway. Curr Eye Res 24:305–312CrossRefPubMedGoogle Scholar
  85. 85.
    Fischer AJ, Omar G, Eubanks J, McGuire CR, Dierks BD, Reh TA (2004) Different aspects of gliosis in retinal Müller glia can be induced by CNTF, insulin and FGF2 in the absence of damage. Mol Vision 10:973–986Google Scholar
  86. 86.
    Stanke JJ, Moose H, El-Hodiri HM, Fischer AJ (2010) A comparative study of Pax2 expression in glial cells in the retinas of birds and mammals. J Comp Neurol 518:2316–2333CrossRefPubMedGoogle Scholar
  87. 87.
    Lewis GP, Fisher SK (2003) Up-regulation of glial fibrillary acidic protein in response to retinal injury: its potential role in glial remodeling and a comparison to vimentin expression. Int Rev Cytol 230:263–290CrossRefPubMedGoogle Scholar
  88. 88.
    Fischer AJ, Zelinka C, Scott MA (2010) Heterogeneity of glia in the retina and optic nerve of birds and mammals. PLoS ONE 5:e10774CrossRefPubMedGoogle Scholar
  89. 89.
    Boije H, Ring H, Lopez-Gallardo M, Prada C, Hallbook F (2010) Pax2 is expressed in a subpopulation of Muller cells in the central chick retina. Dev Dyn 239:1858–1866CrossRefPubMedGoogle Scholar
  90. 90.
    Schulte D, Furukawa T, Peters MA, Kozak CA, Cepko CL (1999) Misexpression of the Emx-related homeobox genes cVax and mVax2 ventralizes the retina and perturbs the retinotectal map. Neuron 24:541–553CrossRefPubMedGoogle Scholar
  91. 91.
    Sehgal R, Karcavich R, Carlson S, Belecky-Adams TL (2008) Ectopic Pax2 expression in chick ventral optic cup phenocopies loss of Pax2 expression. Dev Biol 319:23–33CrossRefPubMedGoogle Scholar
  92. 92.
    Washbourne P, McAllister AK (2002) Techniques for gene transfer into neurons. Curr Opin Neurobiol 12:566–573CrossRefPubMedGoogle Scholar
  93. 93.
    Marquardt T (2003) Transcriptional control of neuronal diversification in the retina. Prog Retin Eye Res 22:567–577CrossRefPubMedGoogle Scholar
  94. 94.
    Sullivan SA, Barthel LK, Largent BL, Raymond PA (1997) A goldfish notch-3 homologue is expressed in neurogenic regions of embryonic, adult, and regenerating brain and retina. Dev Genet 20:208–223CrossRefPubMedGoogle Scholar
  95. 95.
    Dorsky RI, Chang WS, Rapaport DH, Harris WA (1997) Regulation of neuronal diversity in the Xenopus retina by Delta signalling. Nature 385:67–70CrossRefPubMedGoogle Scholar
  96. 96.
    Dorsky RI, Rapaport DH, Harris WA (1995) Xotch inhibits cell differentiation in the Xenopus retina. Neuron 14:487–496CrossRefPubMedGoogle Scholar
  97. 97.
    Furukawa T, Mukherjee S, Bao ZZ, Morrow EM, Cepko CL (2000) rax, Hes1, and notch1 promote the formation of Muller glia by postnatal retinal progenitor cells. Neuron 26:383–394CrossRefPubMedGoogle Scholar
  98. 98.
    Ghai K, Zelinka C, Fischer AJ (2010) Notch signaling influences the neuroprotective and proliferative properties of Müller glia. J Neurosci 30:3101–3112CrossRefPubMedGoogle Scholar
  99. 99.
    Stanke JJ, Fischer AJ (2010) Embryonic retinal progenitors provide trophic support to mature retinal neurons. Invest Ophthalmol Vis Sci 51:2208–2218CrossRefPubMedGoogle Scholar
  100. 100.
    Close JL, Gumuscu B, Reh TA (2005) Retinal neurons regulate proliferation of postnatal progenitors and Muller glia in the rat retina via TGF beta signaling. Development 132:3015–3026CrossRefPubMedGoogle Scholar
  101. 101.
    Osakada F, Ooto S, Akagi T, Mandai M, Akaike A, Takahashi M (2007) Wnt signaling promotes regeneration in the retina of adult mammals. J Neurosci 27:4210–4219CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Neuroscience, College of MedicineThe Ohio State UniversityColumbusUSA
  2. 2.Department of Neuroscience, College of MedicineThe Ohio State UniversityColumbusUSA

Personalised recommendations