Müller glial cell reactivation in Xenopus models of retinal degeneration

Glia. 2017 Aug;65(8):1333-1349. doi: 10.1002/glia.23165. Epub 2017 May 26.

Abstract

A striking aspect of tissue regeneration is its uneven distribution among different animal classes, both in terms of modalities and efficiency. The retina does not escape the rule, exhibiting extraordinary self-repair properties in anamniote species but extremely limited ones in mammals. Among cellular sources prone to contribute to retinal regeneration are Müller glial cells, which in teleosts have been known for a decade to re-acquire a stem/progenitor state and regenerate retinal neurons following injury. As their regenerative potential was hitherto unexplored in amphibians, we tackled this issue using two Xenopus retinal injury paradigms we implemented: a mechanical needle poke injury and a transgenic model allowing for conditional photoreceptor cell ablation. These models revealed that Müller cells are indeed able to proliferate and replace lost cells following damage/degeneration in the retina. Interestingly, the extent of cell cycle re-entry appears dependent on the age of the animal, with a refractory period in early tadpole stages. Our findings pave the way for future studies aimed at identifying the molecular cues that either sustain or constrain the recruitment of Müller glia, an issue of utmost importance to set up therapeutic strategies for eye regenerative medicine.

Keywords: Müller glia; needle poke injury; nitroreductase/metronidazole; photoreceptors; regeneration; retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Genetically Modified
  • Animals, Newborn
  • Bromodeoxyuridine / metabolism
  • Cell Proliferation
  • Diamines / pharmacology
  • Disease Models, Animal
  • Ependymoglial Cells / metabolism
  • Ependymoglial Cells / pathology*
  • Ependymoglial Cells / physiology*
  • Gene Expression Regulation / physiology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Metronidazole / pharmacology
  • Proliferating Cell Nuclear Antigen / metabolism
  • Radiation-Sensitizing Agents / pharmacology
  • Regeneration / physiology
  • Retinal Degeneration / pathology*
  • Retinal Degeneration / physiopathology*
  • Rhodopsin / genetics
  • Rhodopsin / metabolism
  • SOX9 Transcription Factor / metabolism
  • Thiazoles / pharmacology
  • Urea / analogs & derivatives
  • Urea / metabolism
  • Xenopus laevis

Substances

  • 1-(3-dimethylaminopropyl)-3-ethylurea
  • 24-diamino-5-phenylthiazole
  • Diamines
  • Proliferating Cell Nuclear Antigen
  • Radiation-Sensitizing Agents
  • SOX9 Transcription Factor
  • Thiazoles
  • Metronidazole
  • Green Fluorescent Proteins
  • Urea
  • Rhodopsin
  • Bromodeoxyuridine