Skip to main content

Dedifferentiation and Vision System

  • Chapter
  • First Online:
  • 633 Accesses

Abstract

Based on epidemiology evidence, diseases of the cornea, lens, and retina are the three areas with high incidence among the ophthalmological diseases. The eyes are the window of one’s heart, but it is one of the few organs with little cell renewal or regenerative capacity. Owing to exposure to external environment and the pivotal role in vision imaging system, the cornea is the only place where residing cells could maintain integrity and function during the lifetime. The cornea would even restore its function within 24 h against some minor damages or disorders. However, other parts of the eye seldom show any regenerative or self-renewal capacity. The sensitivity of the retina and plasticity of the lens would decline with aging. Cell-based repair and regeneration have been investigated on the lens and retina. The author puts emphasis on the role of cell dedifferentiation in retina and lens regeneration. For the retina, two kinds of cell-based regeneration were described, namely, retina pigment epithelial cell-dependent way and Müller glia-dependent way. As for the lens regeneration, the author enumerates animal models, signal pathways, transcription factors, and several other aspects. Molecular mechanisms account for the largest proportion in both retina and lens regeneration.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Shepherd RK, et al. Visual prostheses for the blind. Trends Biotechnol. 2013;31(10):562–71.

    Article  CAS  PubMed  Google Scholar 

  2. Pearson RA, et al. Restoration of vision after transplantation of photoreceptors. Nature. 2012;485(7396):99–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Boye SE, et al. A comprehensive review of retinal gene therapy. Mol Ther. 2013;21(3):509–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mitsuda S, et al. Tissue interaction between the retinal pigment epithelium and the choroid triggers retinal regeneration of the newt Cynops pyrrhogaster. Dev Biol. 2005;280(1):122–32.

    Article  CAS  PubMed  Google Scholar 

  5. Chiba C, et al. Visual cycle protein RPE65 persists in new retinal cells during retinal regeneration of adult newt. J Comp Neurol. 2006;495(4):391–407.

    Article  CAS  PubMed  Google Scholar 

  6. Susaki K, Chiba C. MEK mediates in vitro neural transdifferentiation of the adult newt retinal pigment epithelium cells: is FGF2 an induction factor? Pigment Cell Res. 2007;20(5):364–79.

    Article  CAS  PubMed  Google Scholar 

  7. Kaneko J, Chiba C. Immunohistochemical analysis of Musashi-1 expression during retinal regeneration of adult newt. Neurosci Lett. 2009;450(3):252–7.

    Article  CAS  PubMed  Google Scholar 

  8. Yoshikawa T, et al. MEK-ERK and heparin-susceptible signaling pathways are involved in cell-cycle entry of the wound edge retinal pigment epithelium cells in the adult newt. Pigment Cell Melanoma Res. 2012;25(1):66–82.

    Article  CAS  PubMed  Google Scholar 

  9. Yurco P, Cameron DA. Responses of Muller glia to retinal injury in adult zebrafish. Vis Res. 2005;45(8):991–1002.

    Article  PubMed  Google Scholar 

  10. Fausett BV, Goldman D. A role for alpha1 tubulin-expressing Muller glia in regeneration of the injured zebrafish retina. J Neurosci. 2006;26(23):6303–13.

    Article  CAS  PubMed  Google Scholar 

  11. Raymond PA, et al. Molecular characterization of retinal stem cells and their niches in adult zebrafish. BMC Dev Biol. 2006;6:36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Fimbel SM, et al. Regeneration of inner retinal neurons after intravitreal injection of ouabain in zebrafish. J Neurosci. 2007;27(7):1712–24.

    Article  CAS  PubMed  Google Scholar 

  13. Thummel R, et al. Characterization of Muller glia and neuronal progenitors during adult zebrafish retinal regeneration. Exp Eye Res. 2008;87(5):433–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Qin Z, Barthel LK, Raymond PA. Genetic evidence for shared mechanisms of epimorphic regeneration in zebrafish. Proc Natl Acad Sci U S A. 2009;106(23):9310–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mochii M, et al. Role of Mitf in differentiation and transdifferentiation of chicken pigmented epithelial cell. Dev Biol. 1998;193(1):47–62.

    Article  CAS  PubMed  Google Scholar 

  16. Araki M, Yamao M, Tsudzuki M. Early embryonic interaction of retinal pigment epithelium and mesenchymal tissue induces conversion of pigment epithelium to neural retinal fate in the silver mutation of the Japanese quail. Develop Growth Differ. 1998;40(2):167–76.

    Article  CAS  Google Scholar 

  17. Park CM, Hollenberg MJ. Induction of retinal regeneration in vivo by growth factors. Dev Biol. 1991;148(1):322–33.

    Article  CAS  PubMed  Google Scholar 

  18. Park CM, Hollenberg MJ. Basic fibroblast growth factor induces retinal regeneration in vivo. Dev Biol. 1989;134(1):201–5.

    Article  CAS  PubMed  Google Scholar 

  19. Fischer AJ, Reh TA. Exogenous growth factors stimulate the regeneration of ganglion cells in the chicken retina. Dev Biol. 2002;251(2):367–79.

    Article  CAS  PubMed  Google Scholar 

  20. Fischer AJ, et al. Insulin and fibroblast growth factor 2 activate a neurogenic program in Muller glia of the chicken retina. J Neurosci. 2002;22(21):9387–98.

    CAS  PubMed  Google Scholar 

  21. Fischer AJ, Reh TA. Muller glia are a potential source of neural regeneration in the postnatal chicken retina. Nat Neurosci. 2001;4(3):247–52.

    Article  CAS  PubMed  Google Scholar 

  22. Ooto S, et al. Potential for neural regeneration after neurotoxic injury in the adult mammalian retina. Proc Natl Acad Sci U S A. 2004;101(37):13654–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Das AV, et al. Neural stem cell properties of Muller glia in the mammalian retina: regulation by notch and Wnt signaling. Dev Biol. 2006;299(1):283–302.

    Article  CAS  PubMed  Google Scholar 

  24. Karl MO, et al. Stimulation of neural regeneration in the mouse retina. Proc Natl Acad Sci U S A. 2008;105(49):19508–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Takeda M, et al. alpha-Aminoadipate induces progenitor cell properties of Muller glia in adult mice. Invest Ophthalmol Vis Sci. 2008;49(3):1142–50.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Pollak J, et al. ASCL1 reprograms mouse Muller glia into neurogenic retinal progenitors. Development. 2013;140(12):2619–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lawrence JM, et al. MIO-M1 cells and similar Muller glial cell lines derived from adult human retina exhibit neural stem cell characteristics. Stem Cells. 2007;25(8):2033–43.

    Article  CAS  PubMed  Google Scholar 

  28. Singhal S, et al. Human Muller glia with stem cell characteristics differentiate into retinal ganglion cell (RGC) precursors in vitro and partially restore RGC function in vivo following transplantation. Stem Cells Transl Med. 2012;1(3):188–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Becker S, et al. Acquisition of RGC phenotype in human Muller glia with stem cell characteristics is accompanied by upregulation of functional nicotinic acetylcholine receptors. Mol Vis. 2013;19:1925–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Hitchcock P, et al. Persistent and injury-induced neurogenesis in the vertebrate retina. Prog Retin Eye Res. 2004;23(2):183–94.

    Article  PubMed  Google Scholar 

  31. Susaki K, et al. Musashi-1, an RNA-binding protein, is indispensable for survival of photoreceptors. Exp Eye Res. 2009;88(3):347–55.

    Article  CAS  PubMed  Google Scholar 

  32. Lopashov GV, Sologub AA. Artificial metaplasia of pigmented epithelium into retina in tadpoles and adult frogs. J Embryol Exp Morphol. 1972;28(3):521–46.

    CAS  PubMed  Google Scholar 

  33. Lopashov GV, Sologub AA. Conversion of the pigmented epithelium of adult frogs into retina under the influence of tadpole retina. Sov J Dev Biol. 1974;4(3):250–6.

    CAS  PubMed  Google Scholar 

  34. Bosco L. Transdifferentiation of ocular tissues in larval Xenopus laevis. Differentiation. 1988;39(1):4–15.

    Article  CAS  PubMed  Google Scholar 

  35. Reh TA, Nagy T. A possible role for the vascular membrane in retinal regeneration in Rana catesbienna tadpoles. Dev Biol. 1987;122(2):471–82.

    Article  CAS  PubMed  Google Scholar 

  36. Sakaguchi DS, Janick LM, Reh TA. Basic fibroblast growth factor (FGF-2) induced transdifferentiation of retinal pigment epithelium: generation of retinal neurons and glia. Dev Dyn. 1997;209(4):387–98.

    Article  CAS  PubMed  Google Scholar 

  37. Arresta E, et al. Pigmented epithelium to retinal transdifferentiation and Pax6 expression in larval Xenopus laevis. J Exp Zool A Comp Exp Biol. 2005;303(11):958–67.

    Article  PubMed  Google Scholar 

  38. Yoshii C, et al. Neural retinal regeneration in the anuran amphibian Xenopus laevis post-metamorphosis: transdifferentiation of retinal pigmented epithelium regenerates the neural retina. Dev Biol. 2007;303(1):45–56.

    Article  CAS  PubMed  Google Scholar 

  39. Kuriyama F, Ueda Y, Araki M. Complete reconstruction of the retinal laminar structure from a cultured retinal pigment epithelium is triggered by altered tissue interaction and promoted by overlaid extracellular matrices. Dev Neurobiol. 2009;69(14):950–8.

    Article  CAS  PubMed  Google Scholar 

  40. Del Rio-Tsonis K, Tsonis PA. Eye regeneration at the molecular age. Dev Dyn. 2003;226(2):211–24.

    Article  PubMed  Google Scholar 

  41. Pittack C, Grunwald GB, Reh TA. Fibroblast growth factors are necessary for neural retina but not pigmented epithelium differentiation in chick embryos. Development. 1997;124(4):805–16.

    CAS  PubMed  Google Scholar 

  42. Spence JR, et al. The hedgehog pathway is a modulator of retina regeneration. Development. 2004;131(18):4607–21.

    Article  CAS  PubMed  Google Scholar 

  43. Galy A, et al. Activated MAPK/ERK kinase (MEK-1) induces transdifferentiation of pigmented epithelium into neural retina. Dev Biol. 2002;248(2):251–64.

    Article  CAS  PubMed  Google Scholar 

  44. Luz-Madrigal A, et al. Reprogramming of the chick retinal pigmented epithelium after retinal injury. BMC Biol. 2014;12:28.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Ma W, et al. Reprogramming retinal pigment epithelium to differentiate toward retinal neurons with Sox2. Stem Cells. 2009;27(6):1376–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yan RT, et al. Neurogenin1 effectively reprograms cultured chick retinal pigment epithelial cells to differentiate toward photoreceptors. J Comp Neurol. 2010;518(4):526–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Carr AJ, et al. The expression of retinal cell markers in human retinal pigment epithelial cells and their augmentation by the synthetic retinoid fenretinide. Mol Vis. 2011;17:1701–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Hu Q, et al. Memory in induced pluripotent stem cells: reprogrammed human retinal-pigmented epithelial cells show tendency for spontaneous redifferentiation. Stem Cells. 2010;28(11):1981–91.

    Article  CAS  PubMed  Google Scholar 

  49. Hu QR, et al. Reprogramming human retinal pigmented epithelial cells to neurons using recombinant proteins. Stem Cells Transl Med. 2014;3(12):1526–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Bernardos RL, et al. Late-stage neuronal progenitors in the retina are radial Muller glia that function as retinal stem cells. J Neurosci. 2007;27(26):7028–40.

    Article  CAS  PubMed  Google Scholar 

  51. Kassen SC, et al. Time course analysis of gene expression during light-induced photoreceptor cell death and regeneration in albino zebrafish. Dev Neurobiol. 2007;67(8):1009–31.

    Article  CAS  PubMed  Google Scholar 

  52. Morris AC, et al. Genetic dissection reveals two separate pathways for rod and cone regeneration in the teleost retina. Dev Neurobiol. 2008;68(5):605–19.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Nagashima M, Barthel LK, Raymond PA. A self-renewing division of zebrafish Muller glial cells generates neuronal progenitors that require N-cadherin to regenerate retinal neurons. Development. 2013;140(22):4510–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Thummel R, et al. Pax6a and Pax6b are required at different points in neuronal progenitor cell proliferation during zebrafish photoreceptor regeneration. Exp Eye Res. 2010;90(5):572–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Lenkowski JR, et al. Retinal regeneration in adult zebrafish requires regulation of TGFbeta signaling. Glia. 2013;61(10):1687–97.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Hafler BP, et al. Transcription factor Olig2 defines subpopulations of retinal progenitor cells biased toward specific cell fates. Proc Natl Acad Sci U S A. 2012;109(20):7882–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Thummel R, et al. Inhibition of Muller glial cell division blocks regeneration of the light-damaged zebrafish retina. Dev Neurobiol. 2008;68(3):392–408.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Ritchey ER, et al. The combination of IGF1 and FGF2 and the induction of excessive ocular growth and extreme myopia. Exp Eye Res. 2012;99:1–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hayes S, et al. Notch signaling regulates regeneration in the avian retina. Dev Biol. 2007;312(1):300–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Fischer AJ, Scott MA, Tuten W. Mitogen-activated protein kinase-signaling stimulates Muller glia to proliferate in acutely damaged chicken retina. Glia. 2009;57(2):166–81.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Ghai K, Zelinka C, Fischer AJ. Notch signaling influences neuroprotective and proliferative properties of mature Muller glia. J Neurosci. 2010;30(8):3101–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bringmann A, et al. Cellular signaling and factors involved in Muller cell gliosis: neuroprotective and detrimental effects. Prog Retin Eye Res. 2009;28(6):423–51.

    Article  CAS  PubMed  Google Scholar 

  63. Reyes-Aguirre LI, et al. Glutamate-induced epigenetic and morphological changes allow rat Muller cell dedifferentiation but not further acquisition of a photoreceptor phenotype. Neuroscience. 2013;254:347–60.

    Article  CAS  PubMed  Google Scholar 

  64. Wan J, et al. Sonic hedgehog promotes stem-cell potential of Muller glia in the mammalian retina. Biochem Biophys Res Commun. 2007;363(2):347–54.

    Article  CAS  PubMed  Google Scholar 

  65. Close JL, et al. Epidermal growth factor receptor expression regulates proliferation in the postnatal rat retina. Glia. 2006;54(2):94–104.

    Article  PubMed  Google Scholar 

  66. Ueki Y, Reh TA. EGF stimulates Muller glial proliferation via a BMP-dependent mechanism. Glia. 2013;61(5):778–89.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Giannelli SG, et al. Adult human Muller glia cells are a highly efficient source of rod photoreceptors. Stem Cells. 2011;29(2):344–56.

    Article  CAS  PubMed  Google Scholar 

  68. Jayaram H, et al. Transplantation of photoreceptors derived from human Muller glia restore rod function in the P23H rat. Stem Cells Transl Med. 2014;3(3):323–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Nelson CM, et al. Tumor necrosis factor-alpha is produced by dying retinal neurons and is required for Muller glia proliferation during Zebrafish retinal regeneration. J Neurosci. 2013;33(15):6524–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hochmann S, et al. Fgf signaling is required for photoreceptor maintenance in the adult Zebrafish retina. PLoS One. 2012;7(1):e30365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wan J, Ramachandran R, Goldman D. HB-EGF is necessary and sufficient for Muller glia dedifferentiation and retina regeneration. Dev Cell. 2012;22(2):334–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Hollborn M, et al. Changes in retinal gene expression in proliferative vitreoretinopathy: glial cell expression of HB-EGF. Mol Vis. 2005;11:397–413.

    CAS  PubMed  Google Scholar 

  73. Close JL, Gumuscu B, Reh TA. Retinal neurons regulate proliferation of postnatal progenitors and Muller glia in the rat retina via TGF beta signaling. Development. 2005;132(13):3015–26.

    Article  CAS  PubMed  Google Scholar 

  74. Fausett BV, Gumerson JD, Goldman D. The proneural basic helix-loop-helix gene ascl1a is required for retina regeneration. J Neurosci. 2008;28(5):1109–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Ramachandran R, Fausett BV, Goldman D. Ascl1a regulates Muller glia dedifferentiation and retinal regeneration through a Lin-28-dependent, let-7 microRNA signalling pathway. Nat Cell Biol. 2010;12(11):1101–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Nelson BR, et al. Acheate-scute like 1 (Ascl1) is required for normal delta-like (Dll) gene expression and notch signaling during retinal development. Dev Dyn. 2009;238(9):2163–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Yu J, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–20.

    Article  CAS  PubMed  Google Scholar 

  78. Ramachandran R, Zhao XF, Goldman D. Ascl1a/Dkk/beta-catenin signaling pathway is necessary and glycogen synthase kinase-3beta inhibition is sufficient for zebrafish retina regeneration. Proc Natl Acad Sci U S A. 2011;108(38):15858–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Meyers JR, et al. beta-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina. Neural Dev. 2012;7:30.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Ramachandran R, Zhao XF, Goldman D. Insm1a-mediated gene repression is essential for the formation and differentiation of Muller glia-derived progenitors in the injured retina. Nat Cell Biol. 2012;14(10):1013–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Nelson BR, et al. Genome-wide analysis of Muller glial differentiation reveals a requirement for notch signaling in postmitotic cells to maintain the glial fate. PLoS One. 2011;6(8):e22817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Bonni A, et al. Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway. Science. 1997;278(5337):477–83.

    Article  CAS  PubMed  Google Scholar 

  83. Zhou Q, et al. A gene regulatory network in mouse embryonic stem cells. Proc Natl Acad Sci U S A. 2007;104(42):16438–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Zhang C, et al. STAT3 activation protects retinal ganglion cell layer neurons in response to stress. Exp Eye Res. 2008;86(6):991–7.

    Article  CAS  PubMed  Google Scholar 

  85. Nelson CM, et al. Stat3 defines three populations of Muller glia and is required for initiating maximal muller glia proliferation in the regenerating zebrafish retina. J Comp Neurol. 2012;520(18):4294–311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Joly S, et al. Pax6-positive Muller glia cells express cell cycle markers but do not proliferate after photoreceptor injury in the mouse retina. Glia. 2011;59(7):1033–46.

    Article  PubMed  Google Scholar 

  87. Osakada F, et al. Wnt signaling promotes regeneration in the retina of adult mammals. J Neurosci. 2007;27(15):4210–9.

    Article  CAS  PubMed  Google Scholar 

  88. Fischer AJ, et al. Mitogen-activated protein kinase-signaling regulates the ability of Muller glia to proliferate and protect retinal neurons against excitotoxicity. Glia. 2009;57(14):1538–52.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Wassmer S, et al. A focus on the optical properties of the regenerated newt lens. PLoS One. 2013;8(8):e70845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Suetsugu-Maki R, et al. Lens regeneration in axolotl: new evidence of developmental plasticity. BMC Biol. 2012;10:103.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Gwon AE, Gruber LJ, Mundwiler KE. A histologic study of lens regeneration in aphakic rabbits. Invest Ophthalmol Vis Sci. 1990;31(3):540–7.

    CAS  PubMed  Google Scholar 

  92. Huang Y, Xie L. Expression of transcription factors and crystallin proteins during rat lens regeneration. Mol Vis. 2010;16:341–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Chow RL, et al. Pax6 induces ectopic eyes in a vertebrate. Development. 1999;126(19):4213–22.

    CAS  PubMed  Google Scholar 

  94. Del Rio-Tsonis K, Washabaugh CH, Tsonis PA. Expression of pax-6 during urodele eye development and lens regeneration. Proc Natl Acad Sci U S A. 1995;92(11):5092–6.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Grogg MW, et al. BMP inhibition-driven regulation of six-3 underlies induction of newt lens regeneration. Nature. 2005;438(7069):858–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Madhavan M, et al. The role of Pax-6 in lens regeneration. Proc Natl Acad Sci U S A. 2006;103(40):14848–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Shaham O, et al. Pax6 is essential for lens fiber cell differentiation. Development. 2009;136(15):2567–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Xie Q, et al. Pax6 interactions with chromatin and identification of its novel direct target genes in lens and forebrain. PLoS One. 2013;8(1):e54507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Oliver G, et al. Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development. 1995;121(12):4045–55.

    CAS  PubMed  Google Scholar 

  100. Oliver G, et al. Ectopic lens induction in fish in response to the murine homeobox gene Six3. Mech Dev. 1996;60(2):233–9.

    Article  CAS  PubMed  Google Scholar 

  101. Carl M, Loosli F, Wittbrodt J. Six3 inactivation reveals its essential role for the formation and patterning of the vertebrate eye. Development. 2002;129(17):4057–63.

    CAS  PubMed  Google Scholar 

  102. Bosco L, Venturini G, Willems D. In vitro lens transdifferentiation of Xenopus laevis outer cornea induced by fibroblast growth factor (FGF). Development. 1997;124(2):421–8.

    CAS  PubMed  Google Scholar 

  103. Fukui L, Henry JJ. FGF signaling is required for lens regeneration in Xenopus laevis. Biol Bull. 2011;221(1):137–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Filoni S, et al. Lens regeneration in larval Xenopus laevis: experimental analysis of the decline in the regenerative capacity during development. Dev Biol. 1997;187(1):13–24.

    Article  CAS  PubMed  Google Scholar 

  105. Bosco L, et al. Lens fibre transdifferentiation in cultured larval Xenopus laevis outer cornea under the influence of neural retina-conditioned medium. Cell Mol Life Sci. 1997;53(11-12):921–8.

    Article  CAS  PubMed  Google Scholar 

  106. McDevitt DS, et al. Fibroblast growth factor receptors and regeneration of the eye lens. Dev Dyn. 1997;208(2):220–6.

    Article  CAS  PubMed  Google Scholar 

  107. Del Rio-Tsonis K, et al. Regulation of lens regeneration by fibroblast growth factor receptor 1. Dev Dyn. 1998;213(1):140–6.

    Article  CAS  PubMed  Google Scholar 

  108. Stump RJ, et al. A role for Wnt/beta-catenin signaling in lens epithelial differentiation. Dev Biol. 2003;259(1):48–61.

    Article  CAS  PubMed  Google Scholar 

  109. Lyu J, Joo CK. Wnt signaling enhances FGF2-triggered lens fiber cell differentiation. Development. 2004;131(8):1813–24.

    Article  CAS  PubMed  Google Scholar 

  110. Hayashi T, Mizuno N, Kondoh H. Determinative roles of FGF and Wnt signals in iris-derived lens regeneration in newt eye. Develop Growth Differ. 2008;50(4):279–87.

    Article  CAS  Google Scholar 

  111. Day RC, Beck CW. Transdifferentiation from cornea to lens in Xenopus laevis depends on BMP signalling and involves upregulation of Wnt signalling. BMC Dev Biol. 2011;11:54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. De Robertis EM, Kuroda H. Dorsal-ventral patterning and neural induction in Xenopus embryos. Annu Rev Cell Dev Biol. 2004;20:285–308.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Tsonis PA, et al. A novel role of the hedgehog pathway in lens regeneration. Dev Biol. 2004;267(2):450–61.

    Article  CAS  PubMed  Google Scholar 

  114. Kerr CL, et al. Activation of the hedgehog signaling pathway in the developing lens stimulates ectopic FoxE3 expression and disruption in fiber cell differentiation. Invest Ophthalmol Vis Sci. 2012;53(7):3316–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Choi JJ, et al. A role for smoothened during murine lens and cornea development. PLoS One. 2014;9(9):e108037.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Kulyk WM, Zalik SE. Synthesis of sulfated glycosaminoglycan in newt iris during lens regeneration. Differentiation. 1982;23(1):29–35.

    Article  CAS  PubMed  Google Scholar 

  117. Kulyk WM, Zalik SE, Dimitrov E. Hyaluronic acid production and hyaluronidase activity in the newt iris during lens regeneration. Exp Cell Res. 1987;172(1):180–91.

    Article  CAS  PubMed  Google Scholar 

  118. Elgert KL, Zalik SE. Fibronectin distribution during cell type conversion in newt lens regeneration. Anat Embryol (Berl). 1989;180(2):131–42.

    Article  CAS  Google Scholar 

  119. Tanaka EM, Drechsel DN, Brockes JP. Thrombin regulates S-phase re-entry by cultured newt myotubes. Curr Biol. 1999;9(15):792–9.

    Article  CAS  PubMed  Google Scholar 

  120. Imokawa Y, Brockes JP. Selective activation of thrombin is a critical determinant for vertebrate lens regeneration. Curr Biol. 2003;13(10):877–81.

    Article  CAS  PubMed  Google Scholar 

  121. Nakamura K, et al. miRNAs in newt lens regeneration: specific control of proliferation and evidence for miRNA networking. PLoS One. 2010;5(8):e12058.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Makarev E, et al. Identification of microRNAs and other small RNAs from the adult newt eye. Mol Vis. 2006;12:1386–91.

    CAS  PubMed  Google Scholar 

  123. Tsonis PA, et al. MicroRNAs and regeneration: Let-7 members as potential regulators of dedifferentiation in lens and inner ear hair cell regeneration of the adult newt. Biochem Biophys Res Commun. 2007;362(4):940–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Maki N, et al. Expression of stem cell pluripotency factors during regeneration in newts. Dev Dyn. 2009;238(6):1613–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.

    Article  CAS  PubMed  Google Scholar 

  126. Bhavsar RB, Tsonis PA. Exogenous Oct-4 inhibits lens transdifferentiation in the newt Notophthalmus viridescens. PLoS One. 2014;9(7):e102510.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer-Verlag GmbH Germany

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Fu, X., Zhao, A., Hu, T. (2018). Dedifferentiation and Vision System. In: Cellular Dedifferentiation and Regenerative Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-56179-9_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-56179-9_7

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-56177-5

  • Online ISBN: 978-3-662-56179-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics