CD200R signaling inhibits pro-angiogenic gene expression by macrophages and suppresses choroidal neovascularization

• Published in: Scientific reports 2013-10, Vol.3 (1), p.3072-3072, Article 3072
• Main Authors: Horie, Shintaro, Robbie, Scott J., Liu, Jian, Wu, Wei-Kang, Ali, Robin R., Bainbridge, James W., Nicholson, Lindsay B., Mochizuki, Manabu, Dick, Andrew D., Copland, David A.
• Format: Article
• Language: English
• Subjects: 13/1; 14/63; 38/77; 38/90; 45/88; 631/250/2520; 631/250/256; 64/60; 692/308/1426; Angiogenesis; Animals; Bone marrow; Choroidal Neovascularization - genetics; Choroidal Neovascularization - metabolism; Choroidal Neovascularization - pathology; Dinoprostone - metabolism; Dinoprostone - pharmacology; Disease Models, Animal; Down-regulation; Enrichment media; Gene Expression; Gene Knockout Techniques; Humanities and Social Sciences; IL-1β; Inflammation; Macrophages; Macrophages - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Mice, Knockout; multidisciplinary; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Phenotype; Prostaglandin E2; Retinal Pigment Epithelium - drug effects; Retinal Pigment Epithelium - metabolism; Rodents; Science; Science (multidisciplinary); Signal Transduction; Translation; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vascularization; Wound healing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep03072

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 (BMMΦ) were used to demonstrate that macrophages lacking this inhibitory receptor exhibit enhanced levels of Vegfa, Arg-1 and Il-1β when stimulated with PGE 2 or RPE-conditioned (PGE 2 -enriched) media. Endothelial tube formation in HUVECs was increased when co-cultured with PGE 2 -conditioned CD200R −/− BMMΦ, and laser-induced choroidal neovascularization was enhanced in CD200R-deficient mice. In corroboration, signaling through CD200R results in the down-regulation of BMMΦ 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.