June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Macrophage Activation by RPE-Derived Exosomes
Author Affiliations & Notes
  • Yiqin Zuo
    Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX
  • Zhen-Yang Zhao
    Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX
  • Pei Xu
    Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX
  • Bo Yu
    Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX
  • Yan Chen
    Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX
  • Jiyang Cai
    Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX
  • Footnotes
    Commercial Relationships Yiqin Zuo, None; Zhen-Yang Zhao, None; Pei Xu, None; Bo Yu, None; Yan Chen, None; Jiyang Cai, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 342. doi:https://doi.org/
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    • Get Citation

      Yiqin Zuo, Zhen-Yang Zhao, Pei Xu, Bo Yu, Yan Chen, Jiyang Cai; Macrophage Activation by RPE-Derived Exosomes. Invest. Ophthalmol. Vis. Sci. 2013;54(15):342. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Altered innate immune responses, such as macrophage recruitment and complement deposition, play key roles in the pathogenesis of age-related macular degeneration (AMD). Exosomes are small membrane vesicles released by various cell types and participate in cell-cell communication. We investigated whether exosomes secreted by the retinal pigment epithelium (RPE) affect macrophage activation and polarization.

Methods: Exosomes were isolated from conditioned media of cultured APRE-19 cells by ultracentrifugation. Both bone marrow-derived mouse macrophages (BMDM) and THP1 human monocytic leukemia cells line were treated with different amounts of exosomes for 24 hours. Markers of activated macrophages were assessed by real time RT-PCR and flow cytometry. CCR7, IL-6, and monocyte chemotactic protein-1 (MCP-1) were used as M1 marker. IL-10 and mannose receptor C type 1 (MRC-1) were used as M2 marker. Immunohistochemistry was performed to stain for an exosome marker protein, CD9, on sections of human AMD eyes.

Results: Cultured THP1 monocytes had undetectable level of M1 and M2 macrophage markers. Exosomes isolated from RPE-conditioned media induced a pro-inflammatory response with remarkably up-regulated mRNA levels of M1 markers, CCR7, IL-6 and MCP-1. Similar responses were achieved in THP-1 cells differentiated with phorbol-12-myristate-13-acetate (PMA) and mouse BMDM. Expression of the M2 marker, MRC-1, was decreased after exposure to exosomes. Increased exosome marker proteins were found in the regions near Bruch’s membrane and drusen of human AMD eyes.

Conclusions: Our study suggests that RPE-derived exosomes activate monocytes/macrophages and polarize them towards the pro-inflammatory subsets. Implications of those mechanisms in the etiology of AMD warrants further investigation.

Keywords: 412 age-related macular degeneration • 557 inflammation • 701 retinal pigment epithelium  
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