Biphasic Role of Tgf-β Signaling during Müller Glia Reprogramming and Retinal Regeneration in Zebrafish

Sharma, Poonam; Gupta, Shivangi; Chaudhary, Mansi; Mitra, Soumitra; Chawla, Bindia; Khursheed, M.; Saran, Navnoor Kaur; Ramachandran, Rajesh

doi:10.1016/j.isci.2019.100817

Cited by 35 publications

(59 citation statements)

References 87 publications

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“…It is interesting to note that WNT inhibition was critical to retinal differentiation in pluripotent retinal determination, indicating the modulation of WNT signaling is integral to retinal programming. In addition to WNT elements, TNF-α and TGFβ are important factors that mediate neurogenesis in zebrafish after injury (Sharma et al, 2020). TNF-α is released by the dying neural cells and is produced by Müller cells as well (Nelson et al, 2013), while TGFβ is released from the ECM by metalloproteases after injury.…”

Section: Müller Cells and Trans-differentiationmentioning

confidence: 99%

“…TNF-α is released by the dying neural cells and is produced by Müller cells as well (Nelson et al, 2013), while TGFβ is released from the ECM by metalloproteases after injury. Both cytokines induce downstream expression of factors such as Achaete-scute homolog 1a (Ascl1a), Signal transducer and activator of transcription 3 (STAT3), and hairy-related 4 (her4.1), all of which are indispensable to NPC propagation from the Müller cell (Ueki et al, 2015a;Sharma et al, 2020). TGFβ also promotes cell-cycle exit of Müller cells after progenitor cell proliferation (Sharma et al, 2020).…”

Section: Müller Cells and Trans-differentiationmentioning

confidence: 99%

“…Both cytokines induce downstream expression of factors such as Achaete-scute homolog 1a (Ascl1a), Signal transducer and activator of transcription 3 (STAT3), and hairy-related 4 (her4.1), all of which are indispensable to NPC propagation from the Müller cell (Ueki et al, 2015a;Sharma et al, 2020). TGFβ also promotes cell-cycle exit of Müller cells after progenitor cell proliferation (Sharma et al, 2020). By understanding these factors, they can be implemented in mammalian retina to stimulate regeneration.…”

Section: Müller Cells and Trans-differentiationmentioning

confidence: 99%

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Pluripotent Stem Cells for the Treatment of Retinal Degeneration: Current Strategies and Future Directions

Ikelle

Al‐Ubaidi

Naash

2020

Front. Cell Dev. Biol.

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Stem cells have been part of the biomedical landscape since the early 1960s. However, the translation of stem cells to effective therapeutics have met significant challenges, especially for retinal diseases. The retina is a delicate and complex architecture of interconnected cells that are steadfastly interdependent. Degenerative mechanisms caused by acquired or inherited diseases disrupt this interconnectivity, devastating the retina and causing severe vision loss in many patients. Consequently, retinal differentiation of exogenous and endogenous stem cells is currently being explored as replacement therapies in the debilitating diseases. In this review, we will examine the mechanisms involved in exogenous stem cells differentiation and the challenges of effective integration to the host retina. Furthermore, we will explore the current advancements in trans-differentiation of endogenous stem cells, primarily Müller glia.

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Section: Müller Cells and Trans-differentiationmentioning

confidence: 99%

Section: Müller Cells and Trans-differentiationmentioning

confidence: 99%

Section: Müller Cells and Trans-differentiationmentioning

confidence: 99%

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Pluripotent Stem Cells for the Treatment of Retinal Degeneration: Current Strategies and Future Directions

Ikelle

Al‐Ubaidi

Naash

2020

Front. Cell Dev. Biol.

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“…Potential candidates to apply such approaches would be Müller glia or other retinal neurons as endogenous sources for RGC regeneration. Approaches could be potentially enhanced by modulation of signaling pathways that have already been shown to control the proliferation and neurogenic potential of Müller glia, such as Notch, JAK/STAT, HIPPO/YAP, EGF, WNT, and TGFß (Wan et al, 2012;Ueki and Reh, 2013;Yao et al, 2016;Hamon et al, 2019;Rueda et al, 2019;Sharma et al, 2020). The combined use of signaling modulators with neurogenic and/or RGC-specific transcription factors together with epigenetic remodeling may offer the optimal recipe.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, it was recently suggested that Hippo/YAP signaling may actively repress the proliferation of Müller glia in mice, and overexpression of a YAP form insensitive to phosphorylation is sufficient to induce Müller cell reprogramming into a highly proliferative cell (Hamon et al, 2019;Rueda et al, 2019). Moreover, activation of TGFß by metalloproteinases can influence Müller glia reprogramming and retina regeneration in zebrafish through multiple targets (Sharma et al, 2020). How all these signaling pathways are integrated is still under debate (Wan and Goldman, 2016;Lahne et al, 2020).…”

Section: Regeneration From Endogenous Sources: Müller Gliamentioning

confidence: 99%

On the Generation and Regeneration of Retinal Ganglion Cells

Oliveira-Valença

Bosco

Vetter

et al. 2020

Front. Cell Dev. Biol.

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Retinal development follows a conserved neurogenic program in vertebrates to orchestrate the generation of specific cell types from multipotent progenitors in sequential but overlapping waves. In this program, retinal ganglion cells (RGCs) are the first cell type generated. RGCs are the final output neurons of the retina and are essential for vision and circadian rhythm. Key molecular steps have been defined in multiple vertebrate species to regulate competence, specification, and terminal differentiation of this cell type. This involves neuronal-specific transcription factor networks, regulators of chromatin dynamics and miRNAs. In mammals, RGCs and their optic nerve axons undergo neurodegeneration and loss in glaucoma and other optic neuropathies, resulting in irreversible vision loss. The incapacity of RGCs and axons to regenerate reinforces the need for the design of efficient RGC replacement strategies. Here we describe the essential molecular pathways for the differentiation of RGCs in vertebrates, as well as experimental manipulations that extend the competence window for generation of this early cell type from late progenitors. We discuss recent advances in regeneration of retinal neurons in vivo in both mouse and zebrafish and discuss possible strategies and barriers to achieving RGC regeneration as a therapeutic approach for vision restoration in blinding diseases such as glaucoma.

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An insight on established retinal injury mechanisms and prevalent retinal stem cell activation pathways in vertebrate models

Sherpa

Hui

2021

Anim Models and Exp Med

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The brain processes visual information when light energy transduces into neural activity in the retina. The close-knit components of the central nervous system (CNS), the brain, and its extension retina are thus the critical players in visual perception, thereby aiding in daily activities. While the brain remains well protected inside the skull, the eyes are quite susceptible to physical injuries and chemical accidents. 1 Furthermore, one's genetic makeup and increasing age also invite multiple numbers of eye diseases such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), glaucoma, etc All this has contributed to the recent "World Reports on vision (2019)," which shows that a whopping 2.2 billion people globally fell victim to visual impairment in the past year. 2 The discovery of the existence of adult retinal stem/progenitor cells among different vertebrate species 3 and its high reparative activity in the case of lower vertebrates has presented us with a possibility to "self-heal" the retina one day. 4 Consequently, high regeneration competent animals, which include the amphibian newts and Xenopus, teleost zebrafish (Danio rerio), and chick are thus being explored 5 to investigate different genetic and epigenetic features, signaling pathways, and factors 6,7 that regulate stem cell activation, thus gradually filling in the gaps of our knowledge of mammals, which appear to be the least competent among the group. 8 With the hope of updating and giving researchers an idea about how these animal models have significantly shaped our understanding of the retinal regeneration process, in this review,

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Biphasic Role of Tgf-β Signaling during Müller Glia Reprogramming and Retinal Regeneration in Zebrafish

Cited by 35 publications

References 87 publications

Pluripotent Stem Cells for the Treatment of Retinal Degeneration: Current Strategies and Future Directions

Pluripotent Stem Cells for the Treatment of Retinal Degeneration: Current Strategies and Future Directions

On the Generation and Regeneration of Retinal Ganglion Cells

An insight on established retinal injury mechanisms and prevalent retinal stem cell activation pathways in vertebrate models

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