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Aires ID, Ribeiro-Rodrigues T, Boia R, et al. Exosomes derived from microglia exposed to elevated pressure amplify the neuroinflammatory response in retinal cells. Glia. 2020;68(12):2705-2724doi: 10.1002/glia.23880.
Aires, I. D., Ribeiro-Rodrigues, T., Boia, R., Catarino, S., Girão, H., Ambrósio, A. F., & Santiago, A. R. (2020). Exosomes derived from microglia exposed to elevated pressure amplify the neuroinflammatory response in retinal cells. Glia, 68(12), 2705-2724. https://doi.org/10.1002/glia.23880
Aires, Inês Dinis, et al. "Exosomes derived from microglia exposed to elevated pressure amplify the neuroinflammatory response in retinal cells." Glia vol. 68,12 (2020): 2705-2724. doi: https://doi.org/10.1002/glia.23880
Aires ID, Ribeiro-Rodrigues T, Boia R, Catarino S, Girão H, Ambrósio AF, Santiago AR. Exosomes derived from microglia exposed to elevated pressure amplify the neuroinflammatory response in retinal cells. Glia. 2020 Dec;68(12):2705-2724. doi: 10.1002/glia.23880. Epub 2020 Jul 09. PMID: 32645245.
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Glia. 2020 Dec;68(12):2705-2724. doi: 10.1002/glia.23880. Epub 2020 Jul 09.

Exosomes derived from microglia exposed to elevated pressure amplify the neuroinflammatory response in retinal cells.

Glia

Inês Dinis Aires, Teresa Ribeiro-Rodrigues, Raquel Boia, Steve Catarino, Henrique Girão, António Francisco Ambrósio, Ana Raquel Santiago

Affiliations

  1. Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
  2. Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal.
  3. Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
  4. Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal.

PMID: 32645245 DOI: 10.1002/glia.23880

Abstract

Glaucoma is a degenerative disease that causes irreversible loss of vision and is characterized by retinal ganglion cell (RGC) loss. Others and we have demonstrated that chronic neuroinflammation mediated by reactive microglial cells plays a role in glaucomatous pathology. Exosomes are extracellular vesicles released by most cells, including microglia, that mediate intercellular communication. The role of microglial exosomes in glaucomatous degeneration remains unknown. Taking the prominent role of microglial exosomes in brain neurodegenerative diseases, we studied the contribution of microglial-derived exosomes to the inflammatory response in experimental glaucoma. Microglial cells were exposed to elevated hydrostatic pressure (EHP), to mimic elevated intraocular pressure, the main risk factor for glaucoma. Naïve microglia (BV-2 cells or retinal microglia) were exposed to exosomes derived from BV-2 cells under EHP conditions (BV-Exo-EHP) or cultured in control pressure (BV-Exo-Control). We found that BV-Exo-EHP increased the production of pro-inflammatory cytokines, promoted retinal microglia motility, phagocytic efficiency, and proliferation. Furthermore, the incubation of primary retinal neural cell cultures with BV-Exo-EHP increased cell death and the production of reactive oxygen species. Exosomes derived from retinal microglia (MG-Exo-Control or MG-Exo-EHP) were injected in the vitreous of C57BL/6J mice. MG-Exo-EHP sustained activation of retinal microglia, mediated cell death, and impacted RGC number. Herein, we show that exosomes derived from retinal microglia have an autocrine function and propagate the inflammatory signal in conditions of elevated pressure, contributing to retinal degeneration in glaucomatous conditions.

© 2020 Wiley Periodicals LLC.

Keywords: exosomes; extracellular vesicles; glaucoma; inflammation; microglia; neurodegeneration; retina

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