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Houda Tahiri, Samy Omri, CHUN YANG, Sylvain Chemtob, Pierre Hardy; Lymphocytic Microparticles Modulate Angiogenic Properties of Macrophages in Laser-induced Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2016;57(12):282.
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© ARVO (1962-2015); The Authors (2016-present)
Choroidal neovascularization (CNV) is the major cause of severe vision loss in which choroidal vessels penetrate retinal pigment epithelium (RPE). The scavenger receptor CD36 mediates antiangiogenic effect, which is highly expressed in RPE, microvascular endothelial cells and macrophages. Previously, we have demonstrated that human T-lymphocyte-derived microparticles (LMPs) are capable of modulating macrophages activities. This study is aimed to determine whether CD36 is involved in LMPs-induced antiangiogenic effect in choroidal angiogenesis.
LMPs were produced from apoptotic human T lymphocytes after treated with actinomycin D. Gene expression in LMPs-treated macrophages was evaluated by quantitative RT-PCR, RNA array and FACS analysis. The uptake experiment was performed to determine the involvement of CD36 receptor. In vivo, the antiangiogenic effect of LMPs was investigated in laser-induced CNV model. Immunohistostaining was performed to reveal the angiogenesis-related factors expression by macrophages in CNV areas. Laser capture micro-dissection using to collect tissues in the CNV regions followed by PCR
LMPs dose-dependently inhibited macrophages cell growth without inducing cell death. LMPs pretreated macrophages increased IL-12, decreased CD206. LMPs-pretreated macrophages exhibited strong inhibitory effect on endothelial cell growth and this effect was associated with decreased expression of proangiogenic factor VEGF and increased antiangiogenic factors TSP-1. LMPs co-localized with Dil-LMPs, and LMPs uptake by macrophages is reduced by 60% after CD36 antibody treatment. This inhibition consequently abrogated the effects of LMPs VEGFa and TSP-1 in macrophages. The role of CD36 in mediating the antiangiogenic effect of LMPs was demonstrated in mice and human choroidal explants. In vivo, intravitreal injection of LMPs significantly suppressed laser-induced CNV this antiangiogenic effect was less effective in CD36 KO mice. In CNV region LMPs significantly induced expression of IL-12 but decreased the expression of VEGF and IL-10. Moreover, we found that JNK-1 expression was increased in LMPs-treated macrophages
The expression of critical angiogenesis-related genes in macrophages was effectively modulated by LMPs, this antiangiogenic effect of LMPs-treated macrophages was largely dependent on CD36.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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