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

ABSTRACT: Ongoing research using cell transplantation and viral-mediated gene therapy has been making progress to restore vision by retinal repair, but targeted delivery and complete cellular integration remain challenging. An alternative approach is to induce endogenous Müller glia (MG) to regenerate lost neurons and photoreceptors, as occurs spontaneously in teleost fish and amphibians. Extracellular vesicles (EVs) can transfer protein and RNA cargo between cells serving as a novel means of cell-cell communication. We conducted an in vivo screen in zebrafish to identify sources of EVs that could induce MG to dedifferentiate and generate proliferating progenitor cells after intravitreal injection into otherwise undamaged zebrafish eyes. Small EVs (sEVs) from C6 glioma cells were the most consistent at inducing MG-derived proliferating cells. Ascl1a expression increased after intravitreal injection of C6 sEVs and knockdown of ascl1a inhibited the induction of proliferation. Proteomic and RNAseq analyses of EV cargo content were performed to begin to identify key factors that might target EVs to MG and initiate retina regeneration.

SUBMITTER: Didiano D

PROVIDER: S-EPMC7655690 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Didiano Dominic D Abner Jessica J JJ Hinger Scott A SA Flickinger Zachary Z Kent Matthew M Clement Margaret A MA Balaiya Sankarathi S Liu Qi Q Dai Xiaozhuan X Levine Edward M EM Patton James G JG

Experimental eye research 20200919

Ongoing research using cell transplantation and viral-mediated gene therapy has been making progress to restore vision by retinal repair, but targeted delivery and complete cellular integration remain challenging. An alternative approach is to induce endogenous Müller glia (MG) to regenerate lost neurons and photoreceptors, as occurs spontaneously in teleost fish and amphibians. Extracellular vesicles (EVs) can transfer protein and RNA cargo between cells serving as a novel means of cell-cell co ...[more]

PMID: 32961174

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Dataset Information

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

Publications

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

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