Notch and wnt signaling mediated rod photoreceptor regeneration by müller cells in adult mammalian retina

Carolina Beltrame del Debbio, Sudha Balasubramanian, Sowmya Parameswaran, Anathbandhu Chaudhuri, Fang Qiu, Iqbal Ahmad

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Background: Evidence emerging from a variety of approaches used in different species suggests that Müller cell function may extend beyond its role of maintaining retinal homeostasis to that of progenitors in the adult retina. Enriched Müller cells in vitro or those that re-enter cell cycle in response to neurotoxin-damage to retina in vivo display multipotential and self-renewing capacities, the cardinal features of stem cells. Methodology/Principal Findings: We demonstrate that Notch and Wnt signaling activate Müller cells through their canonical pathways and that a rare subset of activated Müller cells differentiates along rod photoreceptor lineage in the outer nuclear layer. The differentiation of activated Müller cells along photoreceptor lineage is confirmed by multiple approaches that included Hoechst dye efflux analysis, genetic analysis using retina from Nrl-GFP mice, and lineage tracing using GS-GFP lentivirus in wild type and rd mice in vitro and S334ter rats in vivo. Examination of S334ter rats for head-neck tracking of visual stimuli, a behavioral measure of light perception, demonstrates a significant improvement in light perception in animals treated to activate Müller cells. The number of activated Müller cells with rod photoreceptor phenotype in treated animals correlates with the improvement in their light perception. Conclusion/Significance: In summary, our results provide a proof of principle for non-neurotoxin-mediated activation of Müller cells through Notch and Wnt signaling toward the regeneration of rod photoreceptors.

Original languageEnglish (US)
Article numbere12425
JournalPloS one
Volume5
Issue number8
DOIs
StatePublished - Oct 19 2010

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rods (retina)
Retinal Rod Photoreceptor Cells
retina
Retina
Regeneration
Rats
Animals
Neurotoxins
cells
Stem cells
Light
Coloring Agents
Chemical activation
Display devices
Cells
Lentivirus
Photoreceptor Cells
neurotoxins
rats
Cell Cycle

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Notch and wnt signaling mediated rod photoreceptor regeneration by müller cells in adult mammalian retina. / del Debbio, Carolina Beltrame; Balasubramanian, Sudha; Parameswaran, Sowmya; Chaudhuri, Anathbandhu; Qiu, Fang; Ahmad, Iqbal.

In: PloS one, Vol. 5, No. 8, e12425, 19.10.2010.

Research output: Contribution to journalArticle

del Debbio, Carolina Beltrame ; Balasubramanian, Sudha ; Parameswaran, Sowmya ; Chaudhuri, Anathbandhu ; Qiu, Fang ; Ahmad, Iqbal. / Notch and wnt signaling mediated rod photoreceptor regeneration by müller cells in adult mammalian retina. In: PloS one. 2010 ; Vol. 5, No. 8.
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