Müller Glia as a Source of Neuronal Progenitor Cells to Regenerate the Damaged Zebrafish Retina

  • Craig M. Nelson
  • David R. HydeEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)


In humans, a wide variety of either genetic diseases, such as retinitis pigmentosa and age-related macular degeneration, or environmentally induced damage, such as diabetic retinopathy, rob large numbers of individuals their sight every year. Recently, research in primarily the damaged zebrafish and postnatal chick retinas have highlighted the potential of the Müller glia to serve as an adult stem cell source to regenerate the lost neurons. This work has expanded to study the adult stem cell potential of the rodent and human Müller glia in both the intact retina and cell culture. Unfortunately, mammalian Müller glia appear to have very limited potential to proliferate and differentiate into specific retinal neuronal cell types. This may be due to the mammalian Müller glia either lacking positive regulatory factors to carry out a regenerative response or possessing negative regulatory factors that block regeneration. To better understand what is required for the Müller glia to regenerate damaged retinal neurons, extensive work in the zebrafish retina, which exhibits a robust and highly specific regenerative response, holds much promise at providing the necessary information. In this review, we will explore the current state of knowledge of damage-induced retinal regeneration in zebrafish.


Retinal regeneration Zebrafish Stat3 Ascl1a Pax6 Müller glia Phagocytosis TNFα 


  1. Aaronson DS, Horvath CM (2002) A road map for those who don’t know JAK-STAT. Science 296:1653–1655PubMedCrossRefGoogle Scholar
  2. Bailey TJ, Fossum SL, Fimbel SM et al (2010) The inhibitor of phagocytosis, O-phospho-L-serine, suppresses Müller glia proliferation and cone cell regeneration in the light-damaged zebrafish retina. Exp Eye Res 91:601–612PubMedCrossRefGoogle Scholar
  3. Bernardos RL, Barthel LK, Meyers JR et al (2007) Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells. J Neurosci 27:7028–7040PubMedCrossRefGoogle Scholar
  4. Cameron DA, Carney LH (2000) Cell mosaic patterns in the native and regenerated inner retina of zebrafish: implications for retinal assembly. J Comp Neurol 416:356–367PubMedCrossRefGoogle Scholar
  5. Cameron DA, Gentile KL, Middleton FA et al (2005) Gene expression profiles of intact and regenerating zebrafish retina. Mol Vis 11:775–791PubMedGoogle Scholar
  6. Craig SEL, Thummel R, Ahmed H et al (2010) The zebrafish galectin Drgal1-L2 is expressed by proliferating Müller glia and photoreceptor progenitors and regulates the regeneration of rod photoreceptors. Invest Ophthalmol Vis Sci 51:3244–3252PubMedCrossRefGoogle Scholar
  7. Faillace MP, Julian D, Korenbrot JI (2002) Mitotic activation of proliferative cells in the inner nuclear layer of the mature fish retina: regulatory signals and molecular markers. J Comp Neurol 451:127–141PubMedCrossRefGoogle Scholar
  8. Fausett BV, Goldman D (2006) A role for alpha1 tubulin-expressing Müller glia in regeneration of the injured zebrafish retina. J Neurosci 26:6303–6313PubMedCrossRefGoogle Scholar
  9. Fausett BV, Gumerson JD, Goldman D (2008) The proneural basic helix-loop-helix gene ascl1a is required for retina regeneration. J Neurosci 28:1109–1117PubMedCrossRefGoogle Scholar
  10. Fimbel SM, Montgomery JE, Burket CT et al (2007) Regeneration of inner retinal neurons after intravitreal injection of ouabain in zebrafish. J Neurosci 27:1712–1724PubMedCrossRefGoogle Scholar
  11. Hitchcock PF, Lindsey Myhr KJ, Easter SS Jr et al (1992) Local regeneration in the retina of the goldfish. J Neurobiol 23:187–203PubMedCrossRefGoogle Scholar
  12. Kassen SC, Ramanan V, Montgomery JE et al (2007) Time course analysis of gene expression during light-induced photoreceptor cell death and regeneration in albino zebrafish. Dev Neurobiol 67:1009–1031PubMedCrossRefGoogle Scholar
  13. Kassen SC, Thummel R, Campochiaro LA et al (2009) CNTF induces photoreceptor neuroprotection and Müller glial cell proliferation through two different signaling pathways in the adult zebrafish retina. Exp Eye Res 88:1051–1064PubMedCrossRefGoogle Scholar
  14. MacEwan, D (2002) TNF receptor subtype signalling: differences and cellular consequences. Cell Signal 14:477–492PubMedCrossRefGoogle Scholar
  15. McCurley AT, Callard GV (2010) time course analysis of gene expression patterns in zebrafish eye during optic nerve regeneration. J Exp Neurosci 13:17–33Google Scholar
  16. Miscia S, Marchisio M, Grilli A et al (2002) Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells. Cell Growth Differ 13:13–8PubMedGoogle Scholar
  17. Montgomery JE, Parsons MJ, Hyde DR (2010) A novel model of retinal ablation demonstrates that the origin of regenerated rod photoreceptors is dependent on the extent of damage. J Comp Neurol 518:800–814PubMedCrossRefGoogle Scholar
  18. Qin Z, Barthel LK, Raymond PA (2009) Genetic evidence for shared mechanisms of epimorphic regeneration in zebrafish. Proc Natl Acad Sci USA 106:9310–9315PubMedCrossRefGoogle Scholar
  19. Raymond PA, Barthel LK, Bernardos RL et al (2006) Molecular characterization of retinal stem cells and their niches in adult zebrafish. BMC Dev Biol 6:36PubMedCrossRefGoogle Scholar
  20. Sherpa T, Fimbel SM, Mallory DE et al (2008) Ganglion cell regeneration following whole-retina destruction in zebrafish. Dev Neurobiol 68:166–181PubMedCrossRefGoogle Scholar
  21. Thummel R, Enright JM, Kassen SC et al (2010) Pax6a and Pax6b control novel regulatory points during neuronal progenitor cell proliferation in the regenerating zebrafish retina. Exp Eye Res 90:572–582PubMedCrossRefGoogle Scholar
  22. Thummel R, Kassen SC, Montgomery JE et al (2008) Inhibition of Müller glial cell division blocks regeneration of the light-damaged zebrafish retina. Dev Neurobiol 68:392–408PubMedCrossRefGoogle Scholar
  23. Vihtelic TS, Hyde DR (2000) Light-induced rod and cone cell death and regeneration in the adult albino zebrafish (Danio rerio) retina. J Neurobiol 44:289–307PubMedCrossRefGoogle Scholar
  24. Yurco P, Cameron DA (2005) Responses of Müller glia to retinal injury in adult zebrafish. Vis Res 45:991–1002PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Biological Sciences and the Center for Zebrafish ResearchUniversity of Notre DameNotre DameUSA

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