bFGF and insulin lead to migration of Müller glia to photoreceptor layer in rd1 mouse retina

2021 ◽  
Vol 755 ◽  
pp. 135936
Author(s):  
Manvi Goel ◽  
Narender K. Dhingra
Keyword(s):  
Mouse Retina ◽  
Muller Glia ◽  
Müller Glia ◽  
Photoreceptor Layer ◽  
Rd1 Mouse

scholarly journals The microRNA miR-18a Links Proliferation and Inflammation During Photoreceptor Regeneration in the Injured Zebrafish Retina

2021 ◽  
Author(s):  
Evin Magner ◽  
Pamela Sandoval-Sanchez ◽  
Peter F Hitchcock ◽  
Scott M Taylor
Keyword(s):  
Muller Glia ◽  
Müller Glia ◽  
Wild Type ◽  
Post Injury ◽  
Photoreceptor Layer ◽  
Brdu Labeling ◽  
Key Aspects ◽  
The Brain ◽  
Embryonic Retina

Abstract In mammals, photoreceptor loss causes permanent blindness, but in zebrafish (Danio rerio), Müller glia function as intrinsic stem cells, producing progenitor cells that regenerate photoreceptors and restore vision. MicroRNAs (miRNAs) critically regulate neurogenesis in the brain and retina, but the roles of miRNAs in injury-induced neuronal regeneration are largely unknown. The miRNA miR-18a regulates photoreceptor differentiation in the embryonic retina. The purpose of the current study was to determine the function of miR-18a during injury-induced photoreceptor regeneration. RT-qPCR, in-situ hybridization (ISH) and immunohistochemistry (IHC) showed that miR-18a expression increases throughout the retina by 1-day post-injury (dpi) and continues to increase through 5 dpi. Bromodeoxyuridine (BrdU) labeling showed that at 7 and 10 dpi, when regenerated photoreceptors are normally differentiating, there are more proliferating Müller glia-derived progenitors in homozygous miR-18a mutant (miR-18ami5012) retinas compared with wild type (WT), indicating that miR-18a negatively regulates injury-induced proliferation. At 7 and 10 dpi, miR-18ami5012 retinas have fewer mature photoreceptors than WT, but there is no difference at 14 dpi, revealing that photoreceptor regeneration is delayed. BrdU labeling showed that the excess progenitors in miR-18ami5012 retinas migrate to other retinal layers besides the photoreceptor layer. Inflammation is critical for photoreceptor regeneration and RT-qPCR showed that, in the absence of miR-18a, inflammation is prolonged. Suppressing inflammation with dexamethasone rescues the miR-18ami5012 phenotype. Together, these data show that during injury-induced photoreceptor regeneration, miR-18a regulates proliferation and photoreceptor regeneration by regulating key aspects of the inflammatory response during photoreceptor regeneration in zebrafish.

scholarly journals The circadian clock gene Bmal1 is required to control the timing of retinal neurogenesis and lamination of Müller glia in the mouse retina

2019 ◽  
Vol 33 (8) ◽  
pp. 8745-8758 ◽  
Author(s):  
Onkar B. Sawant ◽  
Vijay K. Jidigam ◽  
Rebecca D. Fuller ◽  
Olivia F. Zucaro ◽  
Cristel Kpegba ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Clock Gene ◽  
Mouse Retina ◽  
Muller Glia ◽  
Müller Glia ◽  
Circadian Clock Gene ◽  
Retinal Neurogenesis

scholarly journals STAT pathway activation limits the Ascl1-mediated chromatin remodeling required for neural regeneration from Müller glia in adult mouse retina

2019 ◽  
Author(s):  
Nikolas L. Jorstad ◽  
Matthew S. Wilken ◽  
Levi Todd ◽  
Paul Nakamura ◽  
Nick Radulovich ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Neural Regeneration ◽  
Mouse Retina ◽  
Binding Motif ◽  
Muller Glia ◽  
Müller Glia ◽  
Rna Seq ◽  
Transgenic Expression ◽  
Pathway Activation ◽  
Stat Pathway

AbstractMüller glia can serve as a source for retinal regeneration in some non-mammalian vertebrates. Recently we found that this process can be induced in mouse Müller glia after injury, by combining transgenic expression of the proneural transcription factor Ascl1 and the HDAC inhibitor TSA. However, new neurons are only generated from a subset of Müller glia in this model, and identifying factors that limit Ascl1-mediated MG reprogramming could potentially make this process more efficient, and potentially useful clinically. One factor that limits neurogenesis in some non-mammalian vertebrates is the STAT pathway activation that occurs in Müller glia in response to injury. In this report, we tested whether injury induced STAT activation hampers the ability of Ascl1 to reprogram Müller glia into retinal neurons. Using a STAT inhibitor, in combination with our previously described reprogramming paradigm, we found a large increase in the ability of Müller glia to generate neurons, similar to those we described previously. Single-cell RNA-seq showed that the progenitor-like cells derived from Ascl1-expressing Müller glia have a higher level of STAT signaling than those that become neurons. Using Ascl1 ChIP-seq and DNase-seq, we found that developmentally inappropriate Ascl1 binding sites (that were unique to the overexpression context) had enrichment for the STAT binding motif. This study provides evidence that STAT pathway activation reduces the efficiency of Ascl1-mediated reprogramming in Müller glia, potentially by directing Ascl1 to inappropriate targets.

Pax6-positive müller glia cells express cell cycle markers but do not proliferate after photoreceptor injury in the mouse retina

Glia ◽  
2011 ◽  
Vol 59 (7) ◽  
pp. 1033-1046 ◽  
Author(s):  
Sandrine Joly ◽  
Vincent Pernet ◽  
Marijana Samardzija ◽  
Christian Grimm
Keyword(s):  
Cell Cycle ◽  
Mouse Retina ◽  
Muller Glia ◽  
Müller Glia ◽  
Glia Cells ◽  
Express Cell

scholarly journals Anatomy and spatial organization of Müller glia in mouse retina

2017 ◽  
Vol 525 (8) ◽  
pp. spc1-spc1 ◽  
Author(s):  
Jingjing Wang ◽  
Matthew L. O’Sullivan ◽  
Dibyendu Mukherjee ◽  
Vanessa M. Puñal ◽  
Sina Farsiu ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Mouse Retina ◽  
Muller Glia ◽  
Müller Glia

scholarly journals STAT Signaling Modifies Ascl1 Chromatin Binding and Limits Neural Regeneration from Muller Glia in Adult Mouse Retina

Cell Reports ◽  
2020 ◽  
Vol 30 (7) ◽  
pp. 2195-2208.e5 ◽  
Author(s):  
Nikolas L. Jorstad ◽  
Matthew S. Wilken ◽  
Levi Todd ◽  
Connor Finkbeiner ◽  
Paul Nakamura ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Neural Regeneration ◽  
Mouse Retina ◽  
Muller Glia ◽  
Chromatin Binding ◽  
Müller Glia ◽  
Stat Signaling

scholarly journals The MicroRNA miR-18a Links Proliferation and Inflammation During Photoreceptor Regeneration in the Injured Zebrafish Retina

2021 ◽  
Author(s):  
Evin Magner ◽  
Pamela Sandoval-Sanchez ◽  
Ashley C Kramer ◽  
Ryan Thummel ◽  
Peter F Hitchcock ◽  
...  
Keyword(s):  
Danio Rerio ◽  
Muller Glia ◽  
Neuronal Regeneration ◽  
Müller Glia ◽  
Post Injury ◽  
Inflammatory Gene Expression ◽  
Photoreceptor Layer ◽  
Dividing Cells ◽  
Morpholino Oligonucleotides

Abstract In mammals, photoreceptor loss causes permanent blindness, but in zebrafish (Danio rerio), photoreceptor loss reprograms Müller glia to function as stem cells, producing progenitors that fully regenerate photoreceptors. MicroRNAs (miRNAs) regulate neurogenesis in the CNS, but the roles of miRNAs in injury-induced neuronal regeneration are largely unknown. In the embryonic zebrafish retina, miRNA miR-18a regulates photoreceptor differentiation. The purpose of the current study was to determine in zebrafish the function of miR-18a during injury-induced photoreceptor regeneration. RT-qPCR, in-situ hybridization and immunohistochemistry showed that miR-18a expression increases throughout the retina by 1-day post-injury (dpi) and increases through 5 dpi. To test miR-18a function during photoreceptor regeneration, we used homozygous miR-18a mutants (miR-18ami5012), and knocked down miR-18a with morpholino oligonucleotides. During photoreceptor regeneration, miR-18ami5012 retinas have fewer mature photoreceptors than WT at 7 and 10 dpi, but there is no difference at 14 dpi, indicating that photoreceptor regeneration is delayed. Labeling dividing cells with bromodeoxyuridine (BrdU) showed that at 7 and 10 dpi, there are excess Müller glia-derived progenitors in both mutants and morphants, indicating that miR-18a negatively regulates injury-induced proliferation. Tracing BrdU-labeled cells showed that in miR-18ami5012 retinas excess progenitors migrate to other retinal layers in addition to the photoreceptor layer. Inflammation is critical for photoreceptor regeneration, and RT-qPCR showed that in miR-18ami5012 retinas, inflammatory gene expression and microglia activation are prolonged. Suppressing inflammation with dexamethasone rescues the miR-18ami5012 phenotype. Together, these data show that during photoreceptor regeneration in zebrafish, miR-18a regulates proliferation and photoreceptor regeneration by regulating the inflammatory response.

scholarly journals The microRNA miR-18a links proliferation and inflammation during photoreceptor regeneration in the injured zebrafish retina

2021 ◽  
Author(s):  
Evin Magner ◽  
Pamela Sandoval-Sanchez ◽  
Peter F Hitchcock ◽  
Scott M Taylor
Keyword(s):  
Muller Glia ◽  
Müller Glia ◽  
Wild Type ◽  
Post Injury ◽  
Photoreceptor Layer ◽  
Brdu Labeling ◽  
Key Aspects ◽  
The Brain ◽  
Embryonic Retina

In mammals, photoreceptor loss causes permanent blindness, but in zebrafish (Danio rerio), Müller glia function as intrinsic stem cells, producing progenitor cells that regenerate photoreceptors and restore vision. MicroRNAs (miRNAs) critically regulate neurogenesis in the brain and retina, but the roles of miRNAs in injury-induced neuronal regeneration are largely unknown. The miRNA miR-18a regulates photoreceptor differentiation in the embryonic retina. The purpose of the current study was to determine the function of miR-18a during injury-induced photoreceptor regeneration. RT-qPCR, in-situ hybridization (ISH) and immunohistochemistry (IHC) showed that miR-18a expression increases throughout the retina by 1-day post-injury (dpi) and continues to increase through 5 dpi. Bromodeoxyuridine (BrdU) labeling showed that at 7 and 10 dpi, when regenerated photoreceptors are normally differentiating, there are more proliferating Müller glia-derived progenitors in homozygous miR-18a mutant (miR-18ami5012) retinas compared with wild type (WT), indicating that miR-18a negatively regulates injury-induced proliferation. At 7 and 10 dpi, miR-18ami5012 retinas have fewer mature photoreceptors than WT, but there is no difference at 14 dpi, revealing that photoreceptor regeneration is delayed. BrdU labeling showed that the excess progenitors in miR-18ami5012 retinas migrate to other retinal layers besides the photoreceptor layer. Inflammation is critical for photoreceptor regeneration and RT-qPCR showed that, in the absence of miR-18a, inflammation is prolonged. Suppressing inflammation with dexamethasone rescues the miR-18ami5012 phenotype. Together, these data show that during injury-induced photoreceptor regeneration, miR-18a regulates proliferation and photoreceptor regeneration by regulating key aspects of the inflammatory response during photoreceptor regeneration in zebrafish.

Sign in / Sign up

Export Citation Format

Share Document