July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Investigation of the Effect of Lymphocyte-derived Microparticles on the Activity of Macrophages in the Mouse Model of Oxygen-induced Retinopathy
Author Affiliations & Notes
  • ChenRongRong Cai
    pharmacology, University of Montreal, Montreal, Quebec, Canada
    CHU-Sainte Justine research center, Montreal, Quebec, Canada
  • Chun Yang
    CHU-Sainte Justine research center, Montreal, Quebec, Canada
  • Pierre Hardy
    CHU-Sainte Justine research center, Montreal, Quebec, Canada
    pharmacology, University of Montreal, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships   ChenRongRong Cai, None; Chun Yang, None; Pierre Hardy, None
  • Footnotes
    Support  Canadian Institutes of Health Research (CIHR) Grant 201603PJT, number of application: 362383
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4076. doi:
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      ChenRongRong Cai, Chun Yang, Pierre Hardy; Investigation of the Effect of Lymphocyte-derived Microparticles on the Activity of Macrophages in the Mouse Model of Oxygen-induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4076.

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

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Abstract

Purpose : Purpose: Our previous studies have demonstrated the strong anti-angiogenic effect of lymphocytic microparticles (LMPs) derived from apoptotic human CEM T lymphocytes. Recently, we indicated the anti-angiogenic effect of LMPs in the laser-induced choroidal neovascularization (NV) model was partially mediated through targeting the activity of macrophages. LMPs converted macrophages phenotype from M2 (pro-angiogenic) to M1 (anti-angiogenic). Nonetheless, the effect of LMPs on macrophages activities in the retina has not been identified. This study is designed to investigate whether the inhibition of retinal NV by LMPs is resulted from the modulation of chemokines expression from retinal cells and consequently interfering macrophages infiltration.

Methods : Methods: Both genders of C57BL/6 postnatal day 7 (P7) mice were used for the Oxygen-induced retinopathy (OIR) model; Mice weight 5.5g~7g on P12 and 7g~8.5g on P17 were included. 1μL of LMPs (10μg/μL) were intravitreally injected on P12, the same volume of PBS to the contralateral eye (N=6/group). P17 retinal flat-mounts stained with lectin or F4/80 were prepared to analyze NV tufts and macrophages infiltration. P14 OIR retinas were collected for ex vivo retinal explants, supernatants collected from retinal explants treated with or without LMPs (50μg/mL) were used for RAW 264.7 and primary macrophages trans-well migration assay. The chemokines mRNA level in vivo and ex vivo were tested by qPCR.

Results : Results: Retinal NV was inhibited in LMPs-treated group (PBS=4.769% vs. LMPs=1.379%); Macrophages infiltration was suppressed by LMPs in vivo (CTL=140±10 vs. LMPs=61±10); RAW 264.7 (CTL=181.67±30 vs. LMPs=66.33±19) and primary macrophages (CTL=308.67±22 vs. LMPs=251.17±30) migration were reduced in vitro. The mRNA level of chemokines VEGF, MCP-1 and SDF-1 were drastically decreased by LMPs both in vivo and ex vivo.

Conclusions : Conclusions: Our results are consistent with our hypothesis that LMPs inhibited pathological retinal NV in the OIR mouse model partially through reducing the chemokines expression which resulted in suppressed macrophages infiltration.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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