Induction of a proliferative response in the zebrafish retina by injection of extracellular vesicles

Didiano, Dominic; Abner, Jessica J.; Hinger, Scott A.; Flickinger, Zachary; Kent, Matthew R.; Clement, Margaret A.; Balaiya, Sankarathi; Liu, Qi; Dai, Xiaozhuan; Levine, Edward M.; Patton, James G.

doi:10.1016/j.exer.2020.108254

Cited by 8 publications

(8 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transfer of miRNAs or other cargo by EVs might play a role in patterning the retina during development and may also be a key part of degeneration and regeneration (Bian et al, 2020 ). Indeed, retina regeneration can be induced by delivery of EVs (Didiano et al, 2020 ). Although EVs were shown to induce the early stages of retina regeneration, the effects were quite modest.…”

Section: Therapeutic Mirnamentioning

confidence: 99%

miRNAs and Müller Glia Reprogramming During Retina Regeneration

Konar

Ferguson

Flickinger

et al. 2021

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

The use of model systems that are capable of robust, spontaneous retina regeneration has allowed for the identification of genetic pathways and components that are required for retina regeneration. Complemented by mouse models in which retina regeneration can be induced after forced expression of key factors, altered chromatin accessibility, or inhibition of kinase/signaling cascades, a clearer picture of the key regulatory events that control retina regeneration is emerging. In all cases, Müller glia (MG) serve as an adult retinal stem cell that must be reprogrammed to allow for regeneration, with the end goal being to understand why regenerative pathways are blocked in mammals, but spontaneous in other vertebrates such as zebrafish. miRNAs have emerged as key gene regulatory molecules that control both development and regeneration in vertebrates. Here, we focus on a small subset of miRNAs that control MG reprogramming during retina regeneration and have the potential to serve as therapeutic targets for treatment of visual disorders and damage.

show abstract

Section: Therapeutic Mirnamentioning

confidence: 99%

miRNAs and Müller Glia Reprogramming During Retina Regeneration

Konar

Ferguson

Flickinger

et al. 2021

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Multiple studies using transgenic reporter lines to label EVs have demonstrated that zebrafish cells produce EVs, and that conserved proteins regulate their biogenesis. For example, EVs are produced by zebrafish cultured melanoma cells, apoptotic epithelial cells, and osteoblasts, and the yolk syncytial layer is a source of circulating EVs in the developing embryo whose secretion is Syntenin-dependent ( Brock et al, 2019 ; Verweij et al, 2019 ; Didiano et al, 2020 ; Kobayashi-Sun et al, 2020 ; Mary et al, 2020 ). Several recent studies suggest that EVs may play a role during zebrafish regeneration.…”

Section: Extracellular Vesicle Research In Other Established and Emer...mentioning

confidence: 99%

“…After myocardial cryoinjury, the number of EC-EVs decrease as a proportion of total EV number, and overall EV size is decreased, suggesting EV production may be modulated by injury in cell-specific ways ( Scott et al, 2021 ). In an effort to determine whether EVs could functionally induce proliferation in the retina, Didiano et al (2020) injected EVs from mammalian stem cells, iPSCs, and cancer cell lines into adult, undamaged retinas. EVs from C6 rat glioma cells increased proliferation of MG-derived cells to the greatest degree.…”

Section: Extracellular Vesicle Research In Other Established and Emer...mentioning

confidence: 99%

“…EVs from C6 rat glioma cells increased proliferation of MG-derived cells to the greatest degree. The authors attributed the mechanism to the transcription factor Ascl1a, which is required for zebrafish retinal regeneration, because ascl1a expression increased after EV administration and ascl1a knockdown abolished EV-induced proliferation ( Fausett et al, 2008 ; Didiano et al, 2020 ). Together, these studies suggest that 1) EVs are produced by a variety of zebrafish cells, including those in blastemas; 2) injury can alter EV production; and 3) EVs may upregulate transcriptional regulators required for reprogramming and regenerative proliferation.…”

Section: Extracellular Vesicle Research In Other Established and Emer...mentioning

confidence: 99%

See 1 more Smart Citation

An Emerging Frontier in Intercellular Communication: Extracellular Vesicles in Regeneration

Avalos

Forsthoefel

2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Regeneration requires cellular proliferation, differentiation, and other processes that are regulated by secreted cues originating from cells in the local environment. Recent studies suggest that signaling by extracellular vesicles (EVs), another mode of paracrine communication, may also play a significant role in coordinating cellular behaviors during regeneration. EVs are nanoparticles composed of a lipid bilayer enclosing proteins, nucleic acids, lipids, and other metabolites, and are secreted by most cell types. Upon EV uptake by target cells, EV cargo can influence diverse cellular behaviors during regeneration, including cell survival, immune responses, extracellular matrix remodeling, proliferation, migration, and differentiation. In this review, we briefly introduce the history of EV research and EV biogenesis. Then, we review current understanding of how EVs regulate cellular behaviors during regeneration derived from numerous studies of stem cell-derived EVs in mammalian injury models. Finally, we discuss the potential of other established and emerging research organisms to expand our mechanistic knowledge of basic EV biology, how injury modulates EV biogenesis, cellular sources of EVs in vivo, and the roles of EVs in organisms with greater regenerative capacity.

show abstract

“…Morpholino knockdown of Asc1a expression prevented the EV-induced response, suggesting that the EVs may act via Ascl1a, a required transcription factor for zebrafish retinal regeneration [ 235 ]. EVs are small vesicular bodies released from cells as a form of cell–cell communication, used in both a locally and distant autocrine or paracrine fashion [ 235 ]. Here, the researchers proposed that the glial origin of C6 cells may produce EVs with membrane and cargo content that target Müller glia.…”

Section: Neuroprotection and Regeneration In Zebrafish Retinal Injmentioning

confidence: 99%

Neurodegeneration, Neuroprotection and Regeneration in the Zebrafish Retina

Stella

Geathers

Weber

et al. 2021

Cells

View full text Add to dashboard Cite

Neurodegenerative retinal diseases, such as glaucoma and diabetic retinopathy, involve a gradual loss of neurons in the retina as the disease progresses. Central nervous system neurons are not able to regenerate in mammals, therefore, an often sought after course of treatment for neuronal loss follows a neuroprotective or regenerative strategy. Neuroprotection is the process of preserving the structure and function of the neurons that have survived a harmful insult; while regenerative approaches aim to replace or rewire the neurons and synaptic connections that were lost, or induce regrowth of damaged axons or dendrites. In order to test the neuroprotective effectiveness or the regenerative capacity of a particular agent, a robust experimental model of retinal neuronal damage is essential. Zebrafish are being used more often in this type of study because their eye structure and development is well-conserved between zebrafish and mammals. Zebrafish are robust genetic tools and are relatively inexpensive to maintain. The large array of functional and behavioral tests available in zebrafish makes them an attractive model for neuroprotection studies. Some common insults used to model retinal disease and study neuroprotection in zebrafish include intense light, chemical toxicity and mechanical damage. This review covers the existing retinal neuroprotection and regeneration literature in the zebrafish and highlights their potential for future studies.

show abstract

Induction of a proliferative response in the zebrafish retina by injection of extracellular vesicles

Cited by 8 publications

References 87 publications

miRNAs and Müller Glia Reprogramming During Retina Regeneration

miRNAs and Müller Glia Reprogramming During Retina Regeneration

An Emerging Frontier in Intercellular Communication: Extracellular Vesicles in Regeneration

Neurodegeneration, Neuroprotection and Regeneration in the Zebrafish Retina

Contact Info

Product

Resources

About