Prospects for the application of Müller glia and their derivatives in retinal regenerative therapies

Eastlake, Karen; Lamb, William D. B.; Luis, Joshua; Khaw, PT; Jayaram, Hari; Limb, G. Astrid

doi:10.1016/j.preteyeres.2021.100970

Cited by 47 publications

(33 citation statements)

References 244 publications

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“…Further morphological studies suggest that the prenatally differentiating MG remain mitotically active, which explains why the early differentiating MG were not birth-dated by 3 H-thymidine labeling (Hollyfield, 1968;Stiemke and Hollyfield, 1995). This is corroborated by the currently well-established perspectives that differentiated MG in the adult mammalian retina can proliferate in vivo under specific pathologic conditions and in vitro (Eastlake et al, 2021).…”

Section: The Formation Of Müller Glia During Retinal Developmentmentioning

confidence: 73%

“…Additionally, Eastlake and colleagues have recently reported the secretion of extracellular vesicles by MG cultured in vitro (Eastlake et al, 2021). These extracellular vesicles carry RNAs coding for neurotrophic factors and microRNAs that regulate axonal/neuronal growth via the PI3K/Akt pathway, which suggest a neuroprotective role/potential of MG.…”

Section: Functions Of Müller Glia In the Retinamentioning

confidence: 99%

“…Furthermore, they can be induced by various cocktails of growth/differentiation factors for differentiation into post-mitotic retinal cells, such as rod- (Giannelli et al, 2011;Jayaram et al, 2014) and RGCprecursors (Singhal et al, 2012). Recently, MG have been found to release a considerable number of extracellular vesicles, which could potentially be harvested for therapeutic applications (Eastlake et al, 2021).…”

Section: Müller Glia For the Treatment Of Retinal Degenerationmentioning

confidence: 99%

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

Too

Simunovic

2021

Front. Cell Dev. Biol.

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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.

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Section: The Formation Of Müller Glia During Retinal Developmentmentioning

confidence: 73%

Section: Functions Of Müller Glia In the Retinamentioning

confidence: 99%

Section: Müller Glia For the Treatment Of Retinal Degenerationmentioning

confidence: 99%

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

Too

Simunovic

2021

Front. Cell Dev. Biol.

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“…In the context of glial biology, chemical screening based approaches have been utilised to identify compounds to enhance oligodendrogenesis and myelination ( Buckley et al, 2010 ; Early et al, 2018 ), regulators of astrocytic function ( Wheeler et al, 2019 ) and glial regulators of nerve regeneration ( Bremer et al, 2017 ). Indeed, the investigation of glial cells in the context of regeneration and disease is now intensely investigated across models ( Hamon et al, 2016 ; Cayre et al, 2021 ) and is a burgeoning aspect of research ( Franklin et al, 2020 ; García-García et al, 2020 ; Eastlake et al, 2021 ; Hammond et al, 2021 ; Schirmer et al, 2021 ) that will form the basis of future reviews. In this piece, however, we will focus on the larger body of work that to date has investigated the development of glial cells in zebrafish, and begun to investigate their fundamental functional roles in the healthy nervous system.…”

Section: The Advantages Of Zebrafish To Study Glial Cellsmentioning

confidence: 99%

Insights Into Central Nervous System Glial Cell Formation and Function From Zebrafish

Neely

Lyons

2021

Front. Cell Dev. Biol.

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The term glia describes a heterogenous collection of distinct cell types that make up a large proportion of our nervous system. Although once considered the glue of the nervous system, the study of glial cells has evolved significantly in recent years, with a large body of literature now highlighting their complex and diverse roles in development and throughout life. This progress is due, in part, to advances in animal models in which the molecular and cellular mechanisms of glial cell development and function as well as neuron-glial cell interactions can be directly studied in vivo in real time, in intact neural circuits. In this review we highlight the instrumental role that zebrafish have played as a vertebrate model system for the study of glial cells, and discuss how the experimental advantages of the zebrafish lend themselves to investigate glial cell interactions and diversity. We focus in particular on recent studies that have provided insight into the formation and function of the major glial cell types in the central nervous system in zebrafish.

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“…In recent years, embryonic stem cells (ESCs) have been widely used as regenerative therapies for treating numerous incurable diseases, such as myocardial infarction, retinal degeneration, diabetes, and blood cancer among others. [1][2][3] Despite the broad application of ESCs in various intractable diseases, there are still many limitations, including the extremely low regenerative efficiency of these cells and difficulties in controlling the differentiation of targets. 4 Therefore, it is important to understand the precise regulation of ESC properties, such as selfrenewal and pluripotency.…”

Section: Introductionmentioning

confidence: 99%

Suppression of transient receptor potential melastatin 7 regulates pluripotency, proliferation, and differentiation of mouse embryonic stem cells via mechanistic target of rapamycin‐extracellular signal‐regulated kinase activation

Kim

Park

Kwon

et al. 2021

J of Cellular Biochemistry

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Mouse embryonic stem cells (mESCs) are a widely used model for their diverse availability in studying early embryonic development and their application in regenerative treatment of various intractable diseases. Transient receptor potential melastatin 7 (Trpm7) regulates Ca2+ as a nonselective ion channel and is essential for early embryonic development; however, the precise role of Trpm7 in mESCs has not been clearly elucidated. In this study, we showed that the inhibition of Trpm7 affects the pluripotency and self‐renewal of mESCs. We found that short hairpin RNA (shRNA)‐mediated suppression of Trpm7 resulted in decreased expression of transcriptional regulators, Oct4 and Sox2, which maintain stemness in mESCs. In addition, Trpm7 knockdown led to alterations in the basic properties of mESCs, such as decreased proliferation, cell cycle arrest at the G0/G1 phase, and increased apoptosis. Furthermore, embryoid body (EB) formation and teratoma formation assays revealed abnormal regulation of differentiation due to Trpm7 knockdown, including the smaller size of EBs, elevated ectodermal differentiation, and diminished endodermal and mesodermal differentiation. We found that EB Day 7 samples displayed decreased intracellular Ca2+ levels compared to those of the scrambled group. Finally, we identified that these alterations induced by Trpm7 knockdown occurred due to decreased phosphorylation of mechanistic target of rapamycin (mTOR) and subsequent activation of extracellular signal‐regulated kinase (ERK) in mESCs. Our findings suggest that Trpm7 could be a novel regulator for maintaining stemness and modulating the differentiation of mESCs.

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Prospects for the application of Müller glia and their derivatives in retinal regenerative therapies

Cited by 47 publications

References 244 publications

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

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

Insights Into Central Nervous System Glial Cell Formation and Function From Zebrafish

Suppression of transient receptor potential melastatin 7 regulates pluripotency, proliferation, and differentiation of mouse embryonic stem cells via mechanistic target of rapamycin‐extracellular signal‐regulated kinase activation

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