1 Scientific RepoRts | 6:37391 | DOI: 10.1038/srep37391 www.nature.com/scientificreports Lymphocytic Microparticles Modulate Angiogenic properties of Macrophages in Laser-induced Choroidal Neovascularization Houda tahiri 1,2 , samy omri 3 , Chun Yang 2 , François Duhamel 1 , suzanne samarani 4 , Ali Ahmad 4 , Mark Vezina 5 , Martin Bussières 6 , elvire Vaucher 7 , przemyslaw sapieha 3,8 , Gilles Hickson 9 , Karim Hammamji 8 , Réjean Lapointe 10 , Francis Rodier 10,11 , sophie tremblay 12,13 , Isabelle Royal 10 , Jean-François Cailhier 10 , sylvain Chemtob 1,2,3,8,14 & pierre Hardy 1,2,14 pathological choroidal neovascularization (CNV) is the common cause of vision loss in patients with age-related macular degeneration (AMD). Macrophages possess potential angiogenic function in CNV. We have demonstrated that human t lymphocyte-derived microparticles (LMps) exert a potent antiangiogenic efect in several pathological neovascularization models. In this study, we investigated the alteration of proangiogenic properties of macrophages by LMps treatment in vitro and in vivo models. LMps regulated the expression of several angiogenesis-related factors in macrophages and consequently stimulated their antiangiogenic efects evidenced by the suppression of the proliferation of human retinal endothelial cells in co-culture experiments. The involvement of CD36 receptor in LMPs uptake by macrophages was demonstrated by in vitro assays and by immunostaining of choroidal fat mounts. In addition, ex vivo experiments showed that CD36 mediates the antiangiogenic efect of LMPs in murine and human choroidal explants. Furthermore, intravitreal injection of LMps in the mouse model of laser-induced CNV signifcantly suppressed CNV in CD36 dependent manner. The results of this study suggested an ability of LMps to alter the gene expression pattern of angiogenesis-related factors in macrophages, which provide important information for a new therapeutic approach for efciently interfering with both vascular and extravascular components of CNV. Lymphocyte-derived microparticles (LMPs) are small membrane microvesicles released from human T lympho- cytes during apoptosis 1,2 . We have established that LMPs exert strong antiangiogenic efect in vivo on corneal neovascularisation, tumor neovascularization 3,4 , and limit neovascularization during the vasoproliferative phase of ischemic retinopathy 5 . Ex vivo, LMPs suppress microvessel sprouting in aortic ring 3 and choroidal explants 6 . Tese efects depended upon on the integrity of the retinal pigment epithelium (RPE) and involved release of pigment epithelium-derived growth factor (PEDF) and p75 neurotrophin receptor (p75NTR) 6 . However, the role 1 Department of Pharmacology, Université de Montréal, Montréal, Qc, canada. 2 Research center cHU Sainte-Justine, Université de Montréal, Montréal, Qc, canada. 3 Research center Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Qc, canada. 4 Departments of Microbiology and immunology, Université de Montréal, Montréal, Qc, canada. 5 charles River Laboratories, Senneville, Montreal, Qc, canada. 6 V&O Services, Saint-Lazare, Qc, canada. 7 School of Optometry, Université de Montréal, Montréal, Qc, canada. 8 Department of Ophthalmology, Université de Montréal, Montréal, Qc, canada. 9 Department of Pathology and cell Biology, Université de Montréal, Montréal, Qc, canada. 10 institut du cancer de Montréal, cRcHUM–centre de Recherche du centre Hospitalier de l’Université de Montréal and Department of Medicine, Université de Montréal, Montréal, Qc, canada. 11 Department of Radiology, Radio-Oncology and nuclear Medicine, Université de Montréal, Montréal, Qc, canada. 12 University of British columbia, Vancouver, Bc, canada. 13 centre for Molecular Medicine and therapeutics, Vancouver, Bc, canada. 14 Department of Pediatrics, Université de Montréal, Montréal, Qc, canada. correspondence and requests for materials should be addressed to P.H. (email: pierre.hardy@recherche-ste-justine.qc.ca) Received: 31 May 2016 accepted: 27 October 2016 Published: 22 November 2016 opeN