Small-Medium Extracellular Vesicles and Their miRNA Cargo in Retinal Health and Degeneration: Mediators of Homeostasis, and Vehicles for Targeted Gene Therapy

Frontiers in Cellular Neuroscience
Yvette WooffRiccardo Natoli

Abstract

Photoreceptor cell death and inflammation are known to occur progressively in retinal degenerative diseases such as age-related macular degeneration (AMD). However, the molecular mechanisms underlying these biological processes are largely unknown. Extracellular vesicles (EV) are essential mediators of cell-to-cell communication with emerging roles in the modulation of immune responses. EVs, including exosomes, encapsulate and transfer microRNA (miRNA) to recipient cells and in this way can modulate the environment of recipient cells. Dysregulation of EVs however is correlated to a loss of cellular homeostasis and increased inflammation. In this work we investigated the role of isolated retinal small-medium sized EV (s-mEV) which includes exosomes in both the healthy and degenerating retina. Isolated s-mEV 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 s-mEV isolated from healthy and damaged retinas. Finally, the effect of exosome inhibition on cell-to-cell miRNA transfer and immune ...Continue Reading

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Citations

Feb 5, 2021·Frontiers in Cell and Developmental Biology·Sabrina CarrellaMarianthi Karali
Feb 14, 2021·International Journal of Molecular Sciences·Elham PishavarSeeram Ramakrishna
Feb 25, 2021·Neuroscience and Biobehavioral Reviews·Shu ZhaoJialin C Zheng
Mar 23, 2021·Pigment Cell & Melanoma Research·Adrian V CioancaMichele C Madigan
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Zhengyu ZhangZizhong Hu
Sep 2, 2021·Molecular Neurodegeneration·Joshua A Chu-TanRiccardo Natoli

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Datasets Mentioned

BETA
PRJNA606092
1

Methods Mentioned

BETA
RNAseq
Dynamic light scattering
electrophoresis
PCA

Software Mentioned

GraphPad
Image Lab
ImageJ
BWA
FastQC
Gene Specific Analysis ( GSA )
Gatan Microscopy Suite
Zetasizer
ggbeeswarm
Partek ® Flow

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