Mar 30, 2020

Exosomes and their miRNA cargo in retinal health and degeneration: mediators of homeostasis, and vehicles for targeted gene therapy.

BioRxiv : the Preprint Server for Biology
Núria Radó-TrillaM.Mar Albà

Abstract

Photoreceptor cell death and inflammation are known to occur progressively in retinal degenerative diseases, however the molecular mechanisms underlying these biological processes are largely unknown. Exosomes are essential mediators of cell-to-cell communication with emerging roles in the modulation of immune responses. Exosomes encapsulate and transfer nucleic acids, including microRNA (miRNA), to recipient cells which in disease may result in dysfunctional immune responses and a loss of homeostatic regulation. In this work we investigated the role of retinal exosomes in both the healthy and degenerating retina. Isolated exosomes from normal retinas were characterized using dynamic light scattering, transmission electron microscopy and western blotting, and quantified across 5 days of photo-oxidative damage-induced degeneration using nanotracking analysis. Small RNAseq was used to characterize the miRNA cargo of retinal exosomes isolated from healthy and damaged retinas. Finally, the effect of exosome inhibition on cell-to-cell miRNA transfer and immune modulation was conducted using systemic daily administration of exosome inhibitor GW4869 and in situ hybridization of exosome-abundant miRNA, miR-124-3p. Electroretinography a...Continue Reading

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Mentioned in this Paper

Vertebrates
Genes
Polyglutamine
Complex (molecular entity)
Transcription, Genetic
PHOX2B gene
Vincristine
Cell Growth
Polyalanine
TF gene

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