Neurotransmitter-Regulated Regeneration in the Zebrafish Retina

Stem Cell Reports. 2017 Apr 11;8(4):831-842. doi: 10.1016/j.stemcr.2017.02.007. Epub 2017 Mar 9.

Abstract

Current efforts to repair damaged or diseased mammalian retinas are inefficient and largely incapable of fully restoring vision. Conversely, the zebrafish retina is capable of spontaneous regeneration upon damage using Müller glia (MG)-derived progenitors. Understanding how zebrafish MG initiate regeneration may help develop new treatments that prompt mammalian retinas to regenerate. We show that inhibition of γ-aminobutyric acid (GABA) signaling facilitates initiation of MG proliferation. GABA levels decrease following damage, and MG are positioned to detect decreased ambient levels and undergo dedifferentiation. Using pharmacological and genetic approaches, we demonstrate that GABAA receptor inhibition stimulates regeneration in undamaged retinas while activation inhibits regeneration in damaged retinas.

Keywords: GABA; Müller glia; regeneration; retina; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Proliferation*
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Receptors, Glutamate / metabolism
  • Regeneration*
  • Retina / cytology
  • Retina / physiology*
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Zebrafish / physiology*
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Receptors, Glutamate
  • gamma-Aminobutyric Acid