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Cited by 103Retinal Development and DisordersNeurogenesis and neuroplasticity mechanismsRetinal Diseases and Treatments

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Notch and Wnt Signaling Mediated Rod Photoreceptor Regeneration by Müller Cells in Adult Mammalian Retina

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Del Debbio, Carolina Beltrame, Balasubramanian, Sudha, Parameswaran, Sowmya, Chaudhuri, Anathbandhu, Qiu, Fang, Ahmad, Iqbal·2010·PLoS ONE
DOI 10.1371/journal.pone.0012425PMC PMC2928741
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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.

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Figure 1 Effects of Notch/Wnt signaling on the activation of enriched Müller cells. (A) Schematic representation of a protocol for examining the effects of Notch and Wnt signaling on the activation of enriched Müller cells by a neurosphere assay (DAPI in blue, GS in red, and BrdU in green). There was a dose-dependent generation of neurospheres (B) and an accompanying increase in levels of Hes1 transcripts (C) when cultured in the presence of Jag1, compared to controls. Similarly, there was a dose-dependent generation of neurospheres (D) and an accompanying increase in levels of Lef1 transcripts (E) when enriched Müller cells were cultured in the presence of Wnt3a, compared to controls. * = p<0.01, ** = p<0.001, *** = p<0.0001.
Figure 1 Effects of Notch/Wnt signaling on the activation of enriched Müller cells. (A) Schematic representation of a protocol for examining the effects of Notch and Wnt signaling on the activation of enriched Müller cells by a neurosphere assay (DAPI in blue, GS in red, and BrdU in green). There was a dose-dependent generation of neurospheres (B) and an accompanying increase in levels of Hes1 transcripts (C) when cultured in the presence of Jag1, compared to controls. Similarly, there was a dose-dependent generation of neurospheres (D) and an accompanying increase in levels of Lef1 transcripts (E) when enriched Müller cells were cultured in the presence of Wnt3a, compared to controls. * = p<0.01, ** = p<0.001, *** = p<0.0001.CC BY · PubMed Central
Figure 2 Effects of Notch/Wnt signaling on the activation of Müller cells in retinal explants. Schematic representation of a protocol for examining the effects of Notch and Wnt signaling on the activation of Müller cells in retinal explants from wild type mouse (PN21) by BrdU-incorporation (A). Immunofluorescence analysis of retinal explants cultured in the presence of Jag1 revealed BrdU+ cells co-expressing GS and Ki67 (inset) (arrows) (B, C) and the proportion of BrdU+GS+ (D) and BrdU+Ki67+ (E) cells increased in a dose-dependent manner, compared to controls. The effects were abrogated in the presence of DAPT. Similarly, immunofluorescence analysis of retinal explants cultured in the presence of Wnt3a revealed BrdU+ cells co-expressing GS and Ki67 (inset) (F, G) and the proportion of BrdU+GS+ (H) and BrdU+Ki67+ (I) cells increased in a dose-dependent manner, compared to controls. The effects were abrogated in the presence of FzdCRD. ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer. Scale = 10 µm. * = p<0.01, ** = p<0.001, *** = p<0.0001.
Figure 2 Effects of Notch/Wnt signaling on the activation of Müller cells in retinal explants. Schematic representation of a protocol for examining the effects of Notch and Wnt signaling on the activation of Müller cells in retinal explants from wild type mouse (PN21) by BrdU-incorporation (A). Immunofluorescence analysis of retinal explants cultured in the presence of Jag1 revealed BrdU+ cells co-expressing GS and Ki67 (inset) (arrows) (B, C) and the proportion of BrdU+GS+ (D) and BrdU+Ki67+ (E) cells increased in a dose-dependent manner, compared to controls. The effects were abrogated in the presence of DAPT. Similarly, immunofluorescence analysis of retinal explants cultured in the presence of Wnt3a revealed BrdU+ cells co-expressing GS and Ki67 (inset) (F, G) and the proportion of BrdU+GS+ (H) and BrdU+Ki67+ (I) cells increased in a dose-dependent manner, compared to controls. The effects were abrogated in the presence of FzdCRD. ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer. Scale = 10 µm. * = p<0.01, ** = p<0.001, *** = p<0.0001.CC BY · PubMed Central
Figure 3 Müller cell activation in retinal explants by Notch and Wnt signaling. Immunofluorescence analysis of retinal explants cultured in the presence of Jag1 (20 µM)+Wnt3a (2.3 nM) revealed BrdU+ cells co-expressing GS and Ki67 (inset) immunoreactivities (arrows) (A, B) and the proportion of BrdU+GS+ and BrdU+Ki67+ increased compared to controls (C). Q-PCR analysis of gene expression revealed increase in levels of transcripts corresponding to Ki67, cyclinD1, Hes1, Hes5 and decrease in p27kip1 transcript levels in Jag1+Wnt3a treated explants, compared to controls (D). ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer. Scale = 10 µm. *** = p<0.0001.
Figure 3 Müller cell activation in retinal explants by Notch and Wnt signaling. Immunofluorescence analysis of retinal explants cultured in the presence of Jag1 (20 µM)+Wnt3a (2.3 nM) revealed BrdU+ cells co-expressing GS and Ki67 (inset) immunoreactivities (arrows) (A, B) and the proportion of BrdU+GS+ and BrdU+Ki67+ increased compared to controls (C). Q-PCR analysis of gene expression revealed increase in levels of transcripts corresponding to Ki67, cyclinD1, Hes1, Hes5 and decrease in p27kip1 transcript levels in Jag1+Wnt3a treated explants, compared to controls (D). ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer. Scale = 10 µm. *** = p<0.0001.CC BY · PubMed Central
Figure 4 Neural properties of Notch and Wnt signaling activated Müller cells. Immunofluorescence analysis of retinal explants cultured in the presence of Jag1 (20 µM)+Wnt3a (2.3 nM) revealed GS+ cells expressing Pax6 immunoreactivities (arrow) (B) whereas such cells were absent in controls (A). Hoechst dye efflux assay revealed SP cells in Jag1+Wnt3a treated retinal explants (D) and in controls (C). Immunofluorescence analysis of SP cells revealed GS+ cells co-expressing immunoreactivities corresponding to BrdU (E), Pax6 (F), and Rx (G). RT-PCR analysis of SP and NSP cells from Jag1+Wnt3a treated retinal explants revealed a differential gene expression with transcripts corresponding to stem cell marker (Abcg2), neural progenitor markers (Nestin and Sox2), cell cycle regulators (CyclinD1 and Ki67), and transducers of Notch (Hes1) and Wnt (Lef1) enriched in SP cells (H). In contrast, p27kip1 transcripts were enriched in NSP cells. ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer, M = Marker, SP = Side Population, NSP = Non-Side Population. Scale = 2.5 µm.
Figure 4 Neural properties of Notch and Wnt signaling activated Müller cells. Immunofluorescence analysis of retinal explants cultured in the presence of Jag1 (20 µM)+Wnt3a (2.3 nM) revealed GS+ cells expressing Pax6 immunoreactivities (arrow) (B) whereas such cells were absent in controls (A). Hoechst dye efflux assay revealed SP cells in Jag1+Wnt3a treated retinal explants (D) and in controls (C). Immunofluorescence analysis of SP cells revealed GS+ cells co-expressing immunoreactivities corresponding to BrdU (E), Pax6 (F), and Rx (G). RT-PCR analysis of SP and NSP cells from Jag1+Wnt3a treated retinal explants revealed a differential gene expression with transcripts corresponding to stem cell marker (Abcg2), neural progenitor markers (Nestin and Sox2), cell cycle regulators (CyclinD1 and Ki67), and transducers of Notch (Hes1) and Wnt (Lef1) enriched in SP cells (H). In contrast, p27kip1 transcripts were enriched in NSP cells. ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer, M = Marker, SP = Side Population, NSP = Non-Side Population. Scale = 2.5 µm.CC BY · PubMed Central
Figure 5 Interactions between Notch and Wnt signaling during the activation of Müller cells. Hoechst dye efflux assay revealed 0.25% of SP cells in total cell dissociates of retinal explants treated with Wnt3a (B), compared to controls (A). The proportion of SP cells decreased to 0.1% in retinal explants treated with Wnt3a+DAPT (C). The proportion of SP cells increased to 0.5% in retinal explants treated with Jag1+Wnt3a (D), which was decreased to 0.1% (E) when DAPT was added to the culture, suggesting a synergistic interaction between Notch and Wnt signaling in the activation of SP cell phenotype in Müller cells (F).
Figure 5 Interactions between Notch and Wnt signaling during the activation of Müller cells. Hoechst dye efflux assay revealed 0.25% of SP cells in total cell dissociates of retinal explants treated with Wnt3a (B), compared to controls (A). The proportion of SP cells decreased to 0.1% in retinal explants treated with Wnt3a+DAPT (C). The proportion of SP cells increased to 0.5% in retinal explants treated with Jag1+Wnt3a (D), which was decreased to 0.1% (E) when DAPT was added to the culture, suggesting a synergistic interaction between Notch and Wnt signaling in the activation of SP cell phenotype in Müller cells (F).CC BY · PubMed Central
Figure 6 Differentiation of activated Müller cells along rod photoreceptor lineage in wild type mice retina in vitro. Schematic representation of a protocol for examining the neurogenic potential of Notch + Wnt signaling activated Müller cells (A). Immunofluorescence analysis of Jag1+Wnt3a treated retinal explants at 4DIV and 8DIV (days in vitro), demonstrates BrdU+ cells preferentially localized in the INL (B) and ONL (C) (arrows), respectively. BrdU+ cells in the ONL at 8DIV co-expressed immunoreactivities corresponding to GS and opsin (D–G) (arrows). Immunofluorescence analysis of cell dissociates from retinal explants at 8DIV revealed BrdU+ cells expressing GS and opsin immunoreactivities (H–K). The proportion of BrdU+, BrdU+GS+ and BrdU+GS+opsin+ cells is given in L. ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer. Scale = 20 µm.
Figure 6 Differentiation of activated Müller cells along rod photoreceptor lineage in wild type mice retina in vitro. Schematic representation of a protocol for examining the neurogenic potential of Notch + Wnt signaling activated Müller cells (A). Immunofluorescence analysis of Jag1+Wnt3a treated retinal explants at 4DIV and 8DIV (days in vitro), demonstrates BrdU+ cells preferentially localized in the INL (B) and ONL (C) (arrows), respectively. BrdU+ cells in the ONL at 8DIV co-expressed immunoreactivities corresponding to GS and opsin (D–G) (arrows). Immunofluorescence analysis of cell dissociates from retinal explants at 8DIV revealed BrdU+ cells expressing GS and opsin immunoreactivities (H–K). The proportion of BrdU+, BrdU+GS+ and BrdU+GS+opsin+ cells is given in L. ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer. Scale = 20 µm.CC BY · PubMed Central
Figure 7 Differentiation of Müller SP cells along rod photoreceptor lineage. Schematic representation of the activation of Müller SP cells and the chase of their fates at the end of the differentiation phase (A). Hoechst dye efflux analysis of Jag1+Wnt3a treated retinal explants at the end of the activated phase (4DIV) revealed 0.5% of SP cells in cell dissociates (B). SP cells were BrdU+GS+ and opsin− (arrow) whereas NSP cells were all BrdU− and some were GS+ (arrows) and some opsin+ (arrowhead) (C). Hoechst dye efflux analysis of Jag1+Wnt3a treated retinal explants at the end of the differentiation phase (8DIV) revealed the absence of SP cells (D). Immunofluorescence analysis of NSP cells revealed BrdU+ GS+ cells, some of which co-expressed opsin immunoreactivities, suggesting that BrdU+ SP cells lost their SP cell phenotype and shifted to NSP where they differentiated along rod photoreceptor lineage (E). Scale = 5 µm.
Figure 7 Differentiation of Müller SP cells along rod photoreceptor lineage. Schematic representation of the activation of Müller SP cells and the chase of their fates at the end of the differentiation phase (A). Hoechst dye efflux analysis of Jag1+Wnt3a treated retinal explants at the end of the activated phase (4DIV) revealed 0.5% of SP cells in cell dissociates (B). SP cells were BrdU+GS+ and opsin− (arrow) whereas NSP cells were all BrdU− and some were GS+ (arrows) and some opsin+ (arrowhead) (C). Hoechst dye efflux analysis of Jag1+Wnt3a treated retinal explants at the end of the differentiation phase (8DIV) revealed the absence of SP cells (D). Immunofluorescence analysis of NSP cells revealed BrdU+ GS+ cells, some of which co-expressed opsin immunoreactivities, suggesting that BrdU+ SP cells lost their SP cell phenotype and shifted to NSP where they differentiated along rod photoreceptor lineage (E). Scale = 5 µm.CC BY · PubMed Central
Figure 8 Lineage tracing of activated Müller cell differentiation along rod photoreceptor lineage. GS-GFP lentivirus transduced retinal explants from wild type mice (PN21) were cultured in the presence of Jag1+Wnt3a for 4 days followed by differentiation for 4 days in the presence of PN1 rat retinal conditioned medium. Immunofluorescence analysis of retinal explant sections (A–C, arrows) and cell dissociates (D–F) at the end of the differentiation phase (8DIV) revealed GFP expressing Müller cells co-expressing opsin. ONL = outer nuclear layer; INL = inner nuclear layer. Scale = 2.5 µm.
Figure 8 Lineage tracing of activated Müller cell differentiation along rod photoreceptor lineage. GS-GFP lentivirus transduced retinal explants from wild type mice (PN21) were cultured in the presence of Jag1+Wnt3a for 4 days followed by differentiation for 4 days in the presence of PN1 rat retinal conditioned medium. Immunofluorescence analysis of retinal explant sections (A–C, arrows) and cell dissociates (D–F) at the end of the differentiation phase (8DIV) revealed GFP expressing Müller cells co-expressing opsin. ONL = outer nuclear layer; INL = inner nuclear layer. Scale = 2.5 µm.CC BY · PubMed Central
Figure 9 Genetic evidence of activated Müller cell differentiation along rod photoreceptor lineage. Retinal explants from Nrl-GFP mice (PN21) were cultured in the presence of Jag1+Wnt3a for 4 days followed by differentiation for 4 days in the presence of PN1 rat retinal conditioned medium. Immunofluorescence analysis of retinal explant sections at the end of the differentiation phase revealed Sox9 expressing Müller cells co-expressing GFP under the influence of rod photoreceptor regulator, Nrl (A–D, arrows). ONL = outer nuclear layer; INL = inner nuclear layer. Scale = 10 µm.
Figure 9 Genetic evidence of activated Müller cell differentiation along rod photoreceptor lineage. Retinal explants from Nrl-GFP mice (PN21) were cultured in the presence of Jag1+Wnt3a for 4 days followed by differentiation for 4 days in the presence of PN1 rat retinal conditioned medium. Immunofluorescence analysis of retinal explant sections at the end of the differentiation phase revealed Sox9 expressing Müller cells co-expressing GFP under the influence of rod photoreceptor regulator, Nrl (A–D, arrows). ONL = outer nuclear layer; INL = inner nuclear layer. Scale = 10 µm.CC BY · PubMed Central
Figure 10 Rod photoreceptor differentiation of activated Müller cells in rd mice in vitro. Retinal explants from rd mice (PN10) were cultured in the presence of Jag1+Wnt3a for 4 days followed by differentiation for 4 days in the presence of PN1 rat retinal conditioned medium. Immunofluorescence analysis of retinal explant sections (A–D, arrows) and cell dissociates (E–H) at the end of the differentiation phase (8DIV) revealed BrdU+GS+ Müller cells co-expressing opsin. Immunofluorescence analysis of sections of retinal explants that were transduced with GS-GFP lentivirus and subjected to differentiation protocol as above revealed GFP expressing cells co-expressing opsin (I-K, arrows). ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer. Scale = 20 µM.
Figure 10 Rod photoreceptor differentiation of activated Müller cells in rd mice in vitro. Retinal explants from rd mice (PN10) were cultured in the presence of Jag1+Wnt3a for 4 days followed by differentiation for 4 days in the presence of PN1 rat retinal conditioned medium. Immunofluorescence analysis of retinal explant sections (A–D, arrows) and cell dissociates (E–H) at the end of the differentiation phase (8DIV) revealed BrdU+GS+ Müller cells co-expressing opsin. Immunofluorescence analysis of sections of retinal explants that were transduced with GS-GFP lentivirus and subjected to differentiation protocol as above revealed GFP expressing cells co-expressing opsin (I-K, arrows). ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer. Scale = 20 µM.CC BY · PubMed Central
Figure 11 Notch and Wnt signaling-mediated activation of Müller cells in S334ter rats in vivo. S334ter rats received intravitreal injections of Jag1+Wnt2b at PN10 and PN11, followed by immunofluorescence, Hoechst dye efflux and Q-PCR analyses on PN 13. Immunofluorescence analysis of retinal sections (A, B, arrows) and cell dissociates revealed the presence of BrdU+ cells co-expressing GS (C, D), whose proportion was significantly higher than in controls (E). Hoechst dye efflux assay revealed a higher proportion of SP cells (3.4%) in Jag1+Wnt2b treated retina, compared to that in controls (1%) (F, G). Q-PCR analysis of gene expression revealed increase in levels of transcripts corresponding to Ki67, cyclinD1, Hes1, Hes5 and decrease in p27kip1 transcript levels in Jag1+Wnt2b treated retina, compared to controls (H). ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer. Scale = 5 µM. *** = p<0.0001.
Figure 11 Notch and Wnt signaling-mediated activation of Müller cells in S334ter rats in vivo. S334ter rats received intravitreal injections of Jag1+Wnt2b at PN10 and PN11, followed by immunofluorescence, Hoechst dye efflux and Q-PCR analyses on PN 13. Immunofluorescence analysis of retinal sections (A, B, arrows) and cell dissociates revealed the presence of BrdU+ cells co-expressing GS (C, D), whose proportion was significantly higher than in controls (E). Hoechst dye efflux assay revealed a higher proportion of SP cells (3.4%) in Jag1+Wnt2b treated retina, compared to that in controls (1%) (F, G). Q-PCR analysis of gene expression revealed increase in levels of transcripts corresponding to Ki67, cyclinD1, Hes1, Hes5 and decrease in p27kip1 transcript levels in Jag1+Wnt2b treated retina, compared to controls (H). ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer. Scale = 5 µM. *** = p<0.0001.CC BY · PubMed Central
Figure 12 Differentiation of activated Müller cells along rod photoreceptor lineage in S334ter rats in vivo. Schematic representation of a protocol for examining the neurogenic potential of Notch + Wnt signaling activated Müller cells in vivo (A). Immunofluorescence analysis of retinal sections (B–E) and cell dissociates (F–I) at the differentiation phase (PN31) revealed BrdU+GS+ Müller cells co-expressing opsin (arrows). Immunofluorescence analysis of sections of retinal that were transduced with GS-GFP lentivirus and subjected to differentiation protocol as above, revealed GFP expressing cells co-expressing opsin (arrows) (J–L). Examination of the optokinetic response by boxplots revealed significant differences between treated and untreated groups at all stages post-treatment. The length of the box represents the interquartile range (the distance between the 25th and 75th percentiles) (M). The horizontal line in the box represents the median. The vertical lines represent the minimum and maximum values of the analysis variables. A correlation analysis between the proportions of BrdU+GS+opsin+ cells in cell dissociates of treated retina and optokinetic response (cycles/degree) of those animals shows a correlation coefficient of 0.83 and p = 0.01 (N). ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer. Scale = 20 µM.
Figure 12 Differentiation of activated Müller cells along rod photoreceptor lineage in S334ter rats in vivo. Schematic representation of a protocol for examining the neurogenic potential of Notch + Wnt signaling activated Müller cells in vivo (A). Immunofluorescence analysis of retinal sections (B–E) and cell dissociates (F–I) at the differentiation phase (PN31) revealed BrdU+GS+ Müller cells co-expressing opsin (arrows). Immunofluorescence analysis of sections of retinal that were transduced with GS-GFP lentivirus and subjected to differentiation protocol as above, revealed GFP expressing cells co-expressing opsin (arrows) (J–L). Examination of the optokinetic response by boxplots revealed significant differences between treated and untreated groups at all stages post-treatment. The length of the box represents the interquartile range (the distance between the 25th and 75th percentiles) (M). The horizontal line in the box represents the median. The vertical lines represent the minimum and maximum values of the analysis variables. A correlation analysis between the proportions of BrdU+GS+opsin+ cells in cell dissociates of treated retina and optokinetic response (cycles/degree) of those animals shows a correlation coefficient of 0.83 and p = 0.01 (N). ONL = outer nuclear layer; INL = inner nuclear layer; GCL = ganglion cell layer. Scale = 20 µM.CC BY · PubMed Central

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  1. S Kamakura, 2004, Hes binding to STAT3 mediates crosstalk., betBiol, 6, 547

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Metadata

Authors
Del Debbio, C. B., Balasubramanian, S., Parameswaran, S., Chaudhuri, A., Qiu, F., & Ahmad, I.
Affiliations
University of Nebraska Medical Center (US)
Corresponding author
Ahmad, Iqbal
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-08-26
Volume
5
Issue
8
Pages
e12425
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0012425
PMC
PMC2928741
OpenAlex
W2075249408
Cited by
103
References
58
Citations by year
2026: 3 · 2025: 3 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 7 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 11 · 2015: 13 · 2014: 10 · 2013: 10 · 2012: 12
FWCI
3.65
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • U.S. Department of Health and Human Services
  • Research to Prevent Blindness
  • Lincy Foundation
  • Nebraska Department of Health and Human Services
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Keywords
Müller cells, Notch signaling, Wnt signaling, retinal stem cells, light perception
MeSH terms
Animals, Mammals, Mice, Inbred C57BL, Regeneration, Retina, Vision, Ocular, Retinal Rod Photoreceptor Cells, Wnt Proteins, Mice, Rats, Receptors, Notch

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