Skip to main content
SpringerLink
Log in
Book cover

Lens Epithelium and Posterior Capsular Opacification pp 131–141Cite as

Lens Regeneration

  • Chapter
  • First Online:

  • 1645 Accesses

Abstract

Lens regeneration after complete lens removal (lentectomy) has mainly been studied in amphibians. Adult newts or axolotl larvae regenerate the lens from the iris while frog tadpoles from the cornea. Transdifferentiation is the term used to describe the cellular and molecular events that underlie lens regeneration, which involves a terminally differentiated tissue (iris) to change and give rise to a different differentiated tissue (lens). This chapter starts with general comparisons among the three amphibians competent for lens regeneration focusing on how these animals have been used as models to study the process. We focus on newt lens regeneration as it can provide a more broad understanding of the process. We concentrate on current knowledge about the mechanism of lens regeneration by presenting the classical histological stages together with molecular signatures that accompany each stage. We address questions regarding the nature of the contributing cells and their relationship to stem cells. We conclude by presenting high-throughput data including the first newt transcriptome and its application during newt lens regeneration. All this information obtained from lower vertebrates is essential for translation research in higher vertebrates where lens regeneration does not occur.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
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. Baddour JA, Sousounis K, Tsonis PA (2012) Organ repair and regeneration: an overview. Birth Defects Res C Embryo Today 96:1–29

    Article  CAS  PubMed  Google Scholar 

  2. Casco-Robles MM, Yamada S, Miura T, Nakamura K, Haynes T, Maki N, Del Rio-Tsonis K, Tsonis PA, Chiba C (2011) Expressing exogenous genes in newts by transgenesis. Nat Protoc 6:600–608

    Article  CAS  PubMed  Google Scholar 

  3. Tsonis PA, Haynes T, Maki N, Nakamura K, Casco-Robles MM, Yamada S, Miura T, Chiba C, Del Rio-Tsonis K (2011) Controlling gene loss of function in newts with emphasis on lens regeneration. Nat Protoc 6:593–599

    Article  CAS  PubMed  Google Scholar 

  4. Freeman G (1963) Lens regeneration from the cornea in Xenopus laevis. J Exp Zool 154:39–65

    Article  CAS  PubMed  Google Scholar 

  5. Brahma SK, McDevitt DS (1974) Ontogeny and localization of the lens crystallins in Xenopus laevis lens regeneration. J Embryol Exp Morphol 32:783–794

    CAS  PubMed  Google Scholar 

  6. Mizuno N, Mochii M, Takahashi TC, Eguchi G, Okada TS (1999) Lens regeneration in Xenopus is not a mere repeat of lens development, with respect to crystallin gene expression. Differentiation 64:143–149

    Article  CAS  PubMed  Google Scholar 

  7. Schaefer JJ, Oliver G, Henry JJ (1999) Conservation of gene expression during embryonic lens formation and cornea-lens transdifferentiation in Xenopus laevis. Dev Dyn 215:308–318

    Article  CAS  PubMed  Google Scholar 

  8. Mizuno N, Ueda Y, Kondoh H (2005) Requirement for betaB1-crystallin promoter of Xenopus laevis in embryonic lens development and lens regeneration. Dev Growth Differ 47:131–140

    Article  CAS  PubMed  Google Scholar 

  9. Wolff G (1895) Entwickelungsphysiologische Studien. I. Die Regeneration der Urodelenlinse. Arch EntwMech Org 1:380–390

    Google Scholar 

  10. Grogg MW, Call MK, Okamoto M, Vergara MN, Del Rio-Tsonis K, Tsonis PA (2005) BMP inhibition-driven regulation of six-3 underlies induction of newt lens regeneration. Nature 438:858–862

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Hayashi T, Mizuno N, Kondoh H (2008) Determinative roles of FGF and Wnt signals in iris-derived lens regeneration in newt eye. Dev Growth Differ 50:279–287

    Article  CAS  PubMed  Google Scholar 

  12. Eguchi G, Eguchi Y, Nakamura K, Yadav MC, Millan JL, Tsonis PA (2011) Regenerative capacity in newts is not altered by repeated regeneration and ageing. Nat Commun 2:384

    Article  PubMed Central  PubMed  Google Scholar 

  13. Inoue T, Inoue R, Tsutsumi R, Tada K, Urata Y, Michibayashi C, Takemura S, Agata K (2012) Lens regenerates by means of similar processes and timeline in adults and larvae of the newt Cynops pyrrhogaster. Dev Dyn 241:1575–1583

    Article  CAS  PubMed  Google Scholar 

  14. Looso M, Preussner J, Sousounis K, Bruckskotten M, Michel CS, Lignelli E, Reinhardt R, Hoeffner S, Krueger M, Tsonis PA, Borchardt T, Braun T (2013) A de novo assembly of the newt transcriptome combined with proteomic validation identifies new protein families expressed during tissue regeneration. Genome Biol 14:R16

    Article  PubMed Central  PubMed  Google Scholar 

  15. Suetsugu-Maki R, Maki N, Nakamura K, Sumanas S, Zhu J, Del Rio-Tsonis K, Tsonis PA (2012) Lens regeneration in axolotl: new evidence of developmental plasticity. BMC Biol 10:103

    Article  PubMed Central  PubMed  Google Scholar 

  16. Henry JJ, Tsonis PA (2010) Molecular and cellular aspects of amphibian lens regeneration. Prog Retin Eye Res 29:543–555

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Sato T (1940) Vergleichende Studien über die Geschwindigkeit der Wolffschen Linsenregeneration bei Triton taeniatus und bei Diemyctylus pyrrhogaster. Arch EntwMech Org 140:570–613

    Article  Google Scholar 

  18. Imokawa Y, Brockes JP (2003) Selective activation of thrombin is a critical determinant for vertebrate lens regeneration. Curr Biol 13:877–881

    Article  CAS  PubMed  Google Scholar 

  19. Godwin JW, Liem KF Jr, Brockes JP (2010) Tissue factor expression in newt iris coincides with thrombin activation and lens regeneration. Mech Dev 127:321–328

    Article  CAS  PubMed  Google Scholar 

  20. Reyer RW (1966) The influence of neural retina and lens on lens regeneration from dorsal iris implants in Triturus viridescens larvae. Dev Biol 14:214–245

    Article  CAS  PubMed  Google Scholar 

  21. Del Rio-Tsonis K, Jung JC, Chiu IM, Tsonis PA (1997) Conservation of fibroblast growth factor function in lens regeneration. Proc Natl Acad Sci U S A 94:13701–13706

    Article  PubMed Central  PubMed  Google Scholar 

  22. McDevitt DS, Brahma SK, Courtois Y, Jeanny JC (1997) Fibroblast growth factor receptors and regeneration of the eye lens. Dev Dyn 208:220–226

    Article  CAS  PubMed  Google Scholar 

  23. Del Rio-Tsonis K, Trombley MT, McMahon G, Tsonis PA (1998) Regulation of lens regeneration by fibroblast growth factor receptor 1. Dev Dyn 213:140–146

    Article  CAS  PubMed  Google Scholar 

  24. Hayashi T, Mizuno N, Ueda Y, Okamoto M, Kondoh H (2004) FGF2 triggers iris-derived lens regeneration in newt eye. Mech Dev 121:519–526

    Article  CAS  PubMed  Google Scholar 

  25. Sousounis K, Michel CS, Bruckskotten M, Maki N, Borchardt T, Braun T, Looso M, Tsonis PA (2013) A microarray analysis of gene expression patterns during early phases of newt lens regeneration. Mol Vis 19:135–145

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Maki N, Takechi K, Sano S, Tarui H, Sasai Y, Agata K (2007) Rapid accumulation of nucleostemin in nucleolus during newt regeneration. Dev Dyn 236:941–950

    Article  CAS  PubMed  Google Scholar 

  27. Maki N, Suetsugu-Maki R, Tarui H, Agata K, Del Rio-Tsonis K, Tsonis PA (2009) Expression of stem cell pluripotency factors during regeneration in newts. Dev Dyn 238:1613–1616

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Maki N, Tsonis PA, Agata K (2010) Changes in global histone modifications during dedifferentiation in newt lens regeneration. Mol Vis 16:1893–1897

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Yamada T, Karasaki S (1963) Nuclear RNA synthesis in newt iris cells engaged in regenerative transformation into lens cells. Dev Biol 6:595–604

    Article  CAS  PubMed  Google Scholar 

  30. Dumont JN, Yamada T (1972) Dedifferentiation of iris epithelial cells. Dev Biol 29:385–401

    Article  CAS  PubMed  Google Scholar 

  31. Del Rio-Tsonis K, Washabaugh CH, Tsonis PA (1995) Expression of pax-6 during urodele eye development and lens regeneration. Proc Natl Acad Sci U S A 92:5092–5096

    Article  PubMed Central  PubMed  Google Scholar 

  32. Madhavan M, Haynes TL, Frisch NC, Call MK, Minich CM, Tsonis PA, Del Rio-Tsonis K (2006) The role of Pax-6 in lens regeneration. Proc Natl Acad Sci U S A 103:14848–14853

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Tsonis PA, Trombley MT, Rowland T, Chandraratna RA, del Rio-Tsonis K (2000) Role of retinoic acid in lens regeneration. Dev Dyn 219:588–593

    Article  CAS  PubMed  Google Scholar 

  34. Tsonis PA, Tsavaris M, Call MK, Chandraratna RA, Del Rio-Tsonis K (2002) Expression and role of retinoic acid receptor alpha in lens regeneration. Dev Growth Differ 44:391–394

    Article  CAS  PubMed  Google Scholar 

  35. Del Rio-Tsonis K, Tomarev SI, Tsonis PA (1999) Regulation of Prox 1 during lens regeneration. Invest Ophthalmol Vis Sci 40:2039–2045

    PubMed  Google Scholar 

  36. Maki N, Suetsugu-Maki R, Sano S, Nakamura K, Nishimura O, Tarui H, Del Rio-Tsonis K, Ohsumi K, Agata K, Tsonis PA (2010) Oocyte-type linker histone B4 is required for transdifferentiation of somatic cells in vivo. FASEB J 24:3462–3467

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Stump RJ, Ang S, Chen Y, von Bahr T, Lovicu FJ, Pinson K, de Iongh RU, Yamaguchi TP, Sassoon DA, McAvoy JW (2003) A role for Wnt/beta-catenin signaling in lens epithelial differentiation. Dev Biol 259:48–61

    Article  CAS  PubMed  Google Scholar 

  38. Hayashi T, Mizuno N, Takada R, Takada S, Kondoh H (2006) Determinative role of Wnt signals in dorsal iris-derived lens regeneration in newt eye. Mech Dev 123:793–800

    Article  CAS  PubMed  Google Scholar 

  39. Kimura Y, Madhavan M, Call MK, Santiago W, Tsonis PA, Lambris JD, Del Rio-Tsonis K (2003) Expression of complement 3 and complement 5 in newt limb and lens regeneration. J Immunol 170:2331–2339

    Article  CAS  PubMed  Google Scholar 

  40. Mizuno N, Agata K, Sawada K, Mochii M, Eguchi G (2002) Expression of crystallin genes in embryonic and regenerating newt lenses. Dev Growth Differ 44:251–256

    Article  CAS  PubMed  Google Scholar 

  41. Mikami Y (1941) Experimental analysis of the Wolffian lens-regeneration in adult newt, Triturus pyrrhogaster. Jpn J Zool 9:269–302

    Google Scholar 

  42. Eguchi G, Shingai R (1971) Cellular analysis on localization of lens forming potency in the newt iris epithelium. Dev Growth Differ 13:337–349

    Article  CAS  PubMed  Google Scholar 

  43. Ito M, Hayashi T, Kuroiwa A, Okamoto M (1999) Lens formation by pigmented epithelial cell reaggregate from dorsal iris implanted into limb blastema in the adult newt. Dev Growth Differ 41:429–440

    Article  CAS  PubMed  Google Scholar 

  44. Makarev E, Call MK, Grogg MW, Atkinson DL, Milash B, Odelberg SJ, Tsonis PA (2007) Gene expression signatures in the newt irises during lens regeneration. FEBS Lett 581:1865–1870

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Roddy M, Fox TP, McFadden JP, Nakamura K, Del Rio-Tsonis K, Tsonis PA (2008) A comparative proteomic analysis during urodele lens regeneration. Biochem Biophys Res Commun 377:275–279

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Maki N, Martinson J, Nishimura O, Tarui H, Meller J, Tsonis PA, Agata K (2010) Expression profiles during dedifferentiation in newt lens regeneration revealed by expressed sequence tags. Mol Vis 16:72–78

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Marioni JC, Mason CE, Mane SM, Stephens M, Gilad Y (2008) RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res 18:1509–1517

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Sousounis K, Looso M, Maki N, Ivester CJ, Braun T, Tsonis PA (2013) Transcriptome analysis of newt lens regeneration reveals distinct gradients in gene expression patterns. PLoS One 8:e61445

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Tsonis PA, Jang W, Del Rio-Tsonis K, Eguchi G (2001) A unique aged human retinal pigmented epithelial cell line useful for studying lens differentiation in vitro. Int J Dev Biol 45:753–758

    CAS  PubMed  Google Scholar 

  50. Yasuda K, Okada TS, Eguchi G, Hayashi M (1978) A demonstration of a switch of cell type in human fetal eye tissues in vitro: pigmented cells of the iris or the retina can transdifferentiate into lens. Exp Eye Res 26:591–595

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology and Center for Tissue Regeneration and Engineering, University of Dayton, Dayton, OH, 45469-2320, USA

    Konstantinos Sousounis, Kenta Nakamura & Panagiotis A. Tsonis

Authors
  1. Konstantinos Sousounis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenta Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Panagiotis A. Tsonis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Panagiotis A. Tsonis .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Wakayama, Japan

    Shizuya Saika

  2. John A. Moran Eye Center University of Utah, Salt Lake City, Utah, USA

    Liliana Werner

  3. School of Medical Sciences Anatomy & Histology, Lens Research Laboratory The University of Sydney, Sydney, New South Wales, Australia

    Frank J. Lovicu

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Japan

About this chapter

Cite this chapter

Sousounis, K., Nakamura, K., Tsonis, P.A. (2014). Lens Regeneration. In: Saika, S., Werner, L., Lovicu, F. (eds) Lens Epithelium and Posterior Capsular Opacification. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54300-8_7

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-54300-8_7

  • Published:

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-54299-5

  • Online ISBN: 978-4-431-54300-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation