A novel model of retinal ablation demonstrates that the extent of rod cell death regulates the origin of the regenerated zebrafish rod photoreceptors

Jacob E. Montgomery, Michael J. Parsons, David R. Hyde

Research output: Contribution to journalArticle

Abstract

The adult zebrafish retina continuously produces rod photoreceptors from infrequent Müller glial cell division, yielding neuronal progenitor cells that migrate to the outer nuclear layer and become rod precursor cells that are committed to differentiate into rods. Retinal damage models suggested that rod cell death induces regeneration from rod precursor cells, whereas loss of any other retinal neurons activates Müller glia proliferation to produce pluripotent neuronal progenitors that can generate any other neuronal cell type in the retina. We tested this hypothesis by creating two transgenic lines that expressed the E. coli nitroreductase enzyme fused to EGFP (NTR-EGFP) in only rods. Treating transgenic adults with metronidazole resulted in two rod cell death models. First, killing all rods throughout the Tg(zop:nfsB-EGFP) nt19 retina induced robust Müller glial proliferation, which yielded clusters of neuronal progenitor cells. In contrast, ablating only a subset of rods across the Tg(zop:nfsB-EGFP)nt20 retina led to rod precursor, but not Müller glial, cell proliferation. We propose that two different criteria determine whether rod cell death will induce a regenerative response from the Müller glia rather than from the resident rod precursor cells in the ONL. First, there must be a large amount of rod cell death to initiate Müller glia proliferation. Second, the rod cell death must be acute, rather than chronic, to stimulate regeneration from the Müller glia. This suggests that the zebrafish retina possesses mechanisms to quantify the amount and timing of rod cell death.

Original languageEnglish (US)
Pages (from-to)800-814
Number of pages15
JournalJournal of Comparative Neurology
Volume518
Issue number6
DOIs
StatePublished - Mar 15 2010

Keywords

  • Metronidazole
  • Müller glia
  • Neuronal progenitor cell
  • Nitroreductase
  • Retinal regeneration
  • Rod precursor cell
  • Stem cell
  • nfsB

ASJC Scopus subject areas

  • Neuroscience(all)

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