scholarly journals Insights on the Regeneration Potential of Müller Glia in the Mammalian Retina

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1957
Author(s):  
Ahmed Salman ◽  
Michelle McClements ◽  
Robert MacLaren
Keyword(s):  
Cell Types ◽  
Neural Progenitors ◽  
Muller Glia ◽  
Müller Glia ◽  
Regeneration Potential ◽  
Regenerative Capacity ◽  
Structural Support ◽  
Potential Source ◽  
Retinal Photoreceptors ◽  
Mammalian Retina

Müller glia, the major glial cell types in the retina, maintain retinal homeostasis and provide structural support to retinal photoreceptors. They also possess regenerative potential that might be used for retinal repair in response to injury or disease. In teleost fish (such as zebrafish), the Müller glia response to injury involves reprogramming events that result in a population of proliferative neural progenitors that can regenerate the injured retina. Recent studies have revealed several important mechanisms for the regenerative capacity of Müller glia in fish, which may shed more light on the mechanisms of Müller glia reprogramming and regeneration in mammals. Mammalian Müller glia can adopt stem cell characteristics, and in response to special conditions, be persuaded to proliferate and regenerate, although their native regeneration potential is limited. In this review, we consider the work to date revealing the regenerative potential of the mammalian Müller glia and discuss whether they are a potential source for cell regeneration therapy in humans.

scholarly journals Retinal Stem/Progenitor Cells Derived From Adult Müller Glia for the Treatment of Retinal Degeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Lay Khoon Too ◽  
Matthew P. Simunovic
Keyword(s):  
Stem Cell ◽  
Teleost Fish ◽  
Cellular Therapy ◽  
Ex Vivo ◽  
Cell Types ◽  
Muller Glia ◽  
Müller Glia ◽  
Regenerative Capacity ◽  
Cell Potential

Over the past two decades, progress in our understanding of glial function has been revolutionary. Within the retina, a subset of glial cells termed the “Müller glia (MG),” have been demonstrated to play key roles in retinal homeostasis, structure and metabolism. Additionally, MG have also been shown to possess the regenerative capacity that varies across species. In teleost fish, MG respond to injury by reprogramming into stem-like cells capable of regenerating lost tissue. The expression of stem/progenitor cell markers has been demonstrated broadly in mammalian MG, including human MG, but their in vivo regenerative capacity appears evolutionarily limited. Advances in stem cell therapy have progressively elucidated critical mechanisms underlying innate MG reprogramming in teleost fish, which have shown promising results when applied to rodents. Furthermore, when cultured ex vivo, MG from mammals can differentiate into several retina cell types. In this review, we will explore the reparative and regenerative potential of MG in cellular therapy approaches, and outline our current understanding of embryonic retinal development, the stem-cell potential of MG in adult vertebrate retina (including human), and microenvironmental cues that guide MG reprogramming.

scholarly journals A high-density narrow-field inhibitory retinal interneuron with direct coupling to Müller glia

2020 ◽  
Author(s):  
William N Grimes ◽  
Didem Göz Aytürk ◽  
Mrinalini Hoon ◽  
Takeshi Yoshimatsu ◽  
Clare Gamlin ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Glial Cells ◽  
Amacrine Cell ◽  
Electrical Coupling ◽  
Amacrine Cells ◽  
Muller Glia ◽  
Müller Glia ◽  
Cell Type ◽  
Mammalian Retina ◽  
Ganglion Neurons

AbstractAmacrine cells are interneurons comprising the most diverse cell type in the mammalian retina. They help encode visual features such as edges or directed motion by mediating excitatory and inhibitory interactions between input (i.e. bipolar) and output (i.e. ganglion) neurons in the inner plexiform layer (IPL). Like other brain regions, the retina also contains glial cells that contribute to neurotransmitter uptake, neurovascular control and metabolic regulation. Here, we report that a previously poorly characterized, but relatively abundant, inhibitory amacrine cell type in the mouse retina is coupled directly to Müller glia. Electron microscopic reconstructions of this amacrine type revealed extensive associations with Müller glia, whose processes often completely ensheathe the neurites of this amacrine cell type. Microinjections of small tracer molecules into the somas of these amacrine cells led to selective labelling of nearby Müller glia, leading us to suggest the name “Müller glia-coupled amacrine cell” or MAC. Our electrophysiological data also indicate that MACs release glycine at conventional chemical synapses with amacrine, bipolar and retinal ganglion cells (RGCs), and viral transsynaptic tracing showed connections to several known RGC types. Visually-evoked responses revealed a strong preference for light increments; these “ON” responses were primarily mediated by excitatory chemical synaptic input and direct electrical coupling to other cells. This initial characterization of the MAC provides the first evidence for neuron-glia coupling in the mammalian retina and identifies the MAC as a potential link between inhibitory processing and glial function.Significance StatementGap junctions between pairs of neurons or glial cells are commonly found throughout the nervous system, and play a myriad of roles including electrical coupling and metabolic exchange. In contrast, gap junctions between neurons and glia cells are rare and poorly understood. Here we report the first evidence for neuron-glia coupling in the mammalian retina, specifically between an abundant (but previously unstudied) inhibitory interneuron and Müller glia.

Turning Müller Glia into Neural Progenitors in the Retina

2010 ◽  
Vol 42 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Andy J. Fischer ◽  
Rachel Bongini
Keyword(s):  
Neural Progenitors ◽  
Muller Glia ◽  
Müller Glia

scholarly journals Neural stem cell properties of Müller glia in the mammalian retina: Regulation by Notch and Wnt signaling

2006 ◽  
Vol 299 (1) ◽  
pp. 283-302 ◽  
Author(s):  
Ani V. Das ◽  
Kavita B. Mallya ◽  
Xing Zhao ◽  
Faraz Ahmad ◽  
Sumitra Bhattacharya ◽  
...  
Keyword(s):  
Stem Cell ◽  
Wnt Signaling ◽  
Neural Stem Cell ◽  
Muller Glia ◽  
Müller Glia ◽  
Mammalian Retina

scholarly journals A Notch-Gli2 axis sustains Hedgehog responsiveness of neural progenitors and Müller glia

2016 ◽  
Vol 411 (1) ◽  
pp. 85-100 ◽  
Author(s):  
Randy Ringuette ◽  
Michael Atkins ◽  
Pamela S. Lagali ◽  
Erin A. Bassett ◽  
Charles Campbell ◽  
...  
Keyword(s):  
Neural Progenitors ◽  
Muller Glia ◽  
Müller Glia

scholarly journals Regulation of Stem Cell Properties of Müller Glia by JAK/STAT and MAPK Signaling in the Mammalian Retina

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Krista M. Beach ◽  
Jianbo Wang ◽  
Deborah C. Otteson
Keyword(s):  
Stem Cells ◽  
Embryonic Stem ◽  
Mapk Signaling ◽  
Muller Glia ◽  
Müller Glia ◽  
Cellular Mechanisms ◽  
Blood Retinal Barrier ◽  
Extrinsic Factors ◽  
Radial Glial Cells ◽  
Mammalian Retina

In humans and other mammals, the neural retina does not spontaneously regenerate, and damage to the retina that kills retinal neurons results in permanent blindness. In contrast to embryonic stem cells, induced pluripotent stem cells, and embryonic/fetal retinal stem cells, Müller glia offer an intrinsic cellular source for regenerative strategies in the retina. Müller glia are radial glial cells within the retina that maintain retinal homeostasis, buffer ion flux associated with phototransduction, and form the blood/retinal barrier within the retina proper. In injured or degenerating retinas, Müller glia contribute to gliotic responses and scar formation but also show regenerative capabilities that vary across species. In the mammalian retina, regenerative responses achieved to date remain insufficient for potential clinical applications. Activation of JAK/STAT and MAPK signaling by CNTF, EGF, and FGFs can promote proliferation and modulate the glial/neurogenic switch. However, to achieve clinical relevance, additional intrinsic and extrinsic factors that restrict or promote regenerative responses of Müller glia in the mammalian retina must be identified. This review focuses on Müller glia and Müller glial-derived stem cells in the retina and phylogenetic differences among model vertebrate species and highlights some of the current progress towards understanding the cellular mechanisms regulating their regenerative response.

scholarly journals NFkB-signaling promotes glial reactivity and suppresses Müller glia-mediated neuron regeneration in the mammalian retina

2021 ◽  
Author(s):  
Isabella Palazzo ◽  
Levi J. Todd ◽  
Thanh V. Hoang ◽  
Thomas A. Reh ◽  
Seth Blackshaw ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Immune Cells ◽  
Muller Glia ◽  
Müller Glia ◽  
Dynamic Expression ◽  
Lower Vertebrates ◽  
Mammalian Retina ◽  
Neuron Regeneration ◽  
Glial Reactivity

AbstractMüller glia (MG) in mammalian retinas are incapable of regenerating neurons after damage, whereas the MG in lower vertebrates regenerate functional neurons. Identification networks that regulate MG-mediated regeneration is key to harnessing the regenerative potential of MG. Here we study how NFkB-signaling influences glial responses to damage and reprogramming of MG into neurons in the rodent retina. We find activation of NFkB and dynamic expression of NFkB-associated genes in MG after damage, however NFkB activity is inhibited by microglia ablation. Knockout of NFkB in MG suppressed the accumulation of immune cells after damage. Inhibition of NFkB following NMDA-damage significantly enhanced the reprogramming of Ascl1-overexpressing MG into neuron-like cells. scRNA-seq of retinal glia following inhibition of NFkB reveals coordination with signaling via TGFβ2 and suppression of NFI and Id transcription factors. Inhibition of Smad3 or Id transcription factors increased numbers of neuron-like cells produced by Ascl1-overexpressing MG. We conclude that NFkB is a key signaling hub that is activated in MG after damage, mediates the accumulation of immune cells, and suppresses the neurogenic potential of MG.

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