| First Author | Horie S | Year | 2013 |
| Journal | Sci Rep | Volume | 3 |
| Pages | 3072 | PubMed ID | 24170042 |
| Mgi Jnum | J:207783 | Mgi Id | MGI:5559634 |
| Doi | 10.1038/srep03072 | Citation | Horie S, et al. (2013) CD200R signaling inhibits pro-angiogenic gene expression by macrophages and suppresses choroidal neovascularization. Sci Rep 3:3072 |
| abstractText | Macrophages are rapidly conditioned by cognate and soluble signals to acquire phenotypes that deliver specific functions during inflammation, wound healing and angiogenesis. Whether inhibitory CD200R signaling regulates pro-angiogenic macrophage phenotypes with the potential to suppress ocular neovascularization is unknown. CD200R-deficient bone marrow derived macrophages (BMMPhi) were used to demonstrate that macrophages lacking this inhibitory receptor exhibit enhanced levels of Vegfa, Arg-1 and Il-1beta when stimulated with PGE2 or RPE-conditioned (PGE2-enriched) media. Endothelial tube formation in HUVECs was increased when co-cultured with PGE2-conditioned CD200R(-/-) BMMPhi, and laser-induced choroidal neovascularization was enhanced in CD200R-deficient mice. In corroboration, signaling through CD200R results in the down-regulation of BMMPhi angiogenic and pro-inflammatory phenotypes. Translational potential of this pathway was investigated in the laser-induced model of choroidal neovascularization. Local delivery of a CD200R agonist mAb to target myeloid infiltrate alters macrophage phenotype and inhibits pro-angiogenic gene expression, which suppresses pathological angiogenesis and CNV development. |
