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J Cell Mol Med. 2016 Aug;20(8):1457-66. doi: 10.1111/jcmm.12834. Epub 2016 Mar 21.

Oxidative stress in retinal pigment epithelium cells increases exosome secretion and promotes angiogenesis in endothelial cells.

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School of Medicine, Catholic University of Valencia, Valencia, Spain.
Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
Experimental Research Unit, General University Hospital of Albacete, Albacete, Spain.
Valencian Biomedicine Institute CSIC, Valencia, Spain.
Department of Physiology, University of Valencia, Valencia, Spain.
Department of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutive Biology, University of Valencia, Paterna, Valencia, Spain.
Department of Surgery, University of Valencia, Valencia, Spain.


The retinal pigment epithelium (RPE), a monolayer located between the photoreceptors and the choroid, is constantly damaged by oxidative stress, particularly because of reactive oxygen species (ROS). As the RPE, because of its physiological functions, is essential for the survival of the retina, any sustained damage may consequently lead to loss of vision. Exosomes are small membranous vesicles released into the extracellular medium by numerous cell types, including RPE cells. Their cargo includes genetic material and proteins, making these vesicles essential for cell-to-cell communication. Exosomes may fuse with neighbouring cells influencing their fate. It has been observed that RPE cells release higher amounts of exosomes when they are under oxidative stress. Exosomes derived from cultured RPE cells were isolated by ultracentrifugation and quantified by flow cytometry. VEGF receptors (VEGFR) were analysed by both flow cytometry and Western blot. RT-PCR and qPCR were conducted to assess mRNA content of VEGFRs in exosomes. Neovascularization assays were performed after applying RPE exosomes into endothelial cell cultures. Our results showed that stressed RPE cells released a higher amount of exosomes than controls, with a higher expression of VEGFR in the membrane, and enclosed an extra cargo of VEGFR mRNA. Angiogenesis assays confirmed that endothelial cells increased their tube formation capacity when exposed to stressed RPE exosomes.


VEGF receptors; angiogenesis; exosomes; oxidative stress; retinal pigment epithelium

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