title: M2 Macrophages Enhance Pathological Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy.
abstract: OBJECTIVE
  To investigate the roles played by M2 macrophages in a mouse model of oxygen-induced retinopathy (OIR).
  
  
  METHODS
  Oxygen-induced retinopathy was induced in C57BL/6J mice by exposing postnatal day seven (P7) pups to 75% oxygen and then returning them to room air at P12. Real-time RT-PCR and immunofluorescence staining were used to assess the levels and distributions of different macrophage markers. Bone marrow-derived M1 and M2 macrophages and mannosylated clodronate liposomes (MCLs) were injected into the vitreous on P12 to examine the effects at P17. M2 macrophages were cocultured with human retinal endothelial cells (HRECs) to examine their effects on proliferation and tube formation.
  
  
  RESULTS
  The results showed that the M2 macrophages, rather than M1 phenotype, were highly expressed in OIR mice. The number of M2 macrophages had increased significantly at P17, and the increase was closely associated with the presence of neovascular tufts in the OIR retinas. Selective depletion of M2 macrophages suppressed the pathological neovascularization and promoted physiological revascularization. In contrast, intravitreal injection of bone marrow-derived M2 macrophages or the culture supernatants promoted pathological neovascularization and inhibited physiological revascularization. In an in vitro coculture system, M2-polarized macrophages significantly promoted proliferation and tube formation of HRECs.
  
  
  CONCLUSIONS
  These results indicated that M2 macrophages, rather than M1, play an important role in promoting retinal pathological neovascularization probably by producing secreted factors. Thus, targeting M2 macrophages could be a potential therapeutic option for inhibiting retinal pathological neovascularization.
authors.affiliation: Department of Ophthalmology Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Yedi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Ophthalmology Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nakao
authors.affiliation: Department of Ophthalmology Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Yoshimura
authors.affiliation: Department of Ophthalmology Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Ophthalmology Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Nakama
authors.affiliation: Department of Ophthalmology Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kohta
authors.initials: K
authors.lastname: Miyawaki
authors.affiliation: Department of Ophthalmology Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Muneo
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Department of Ophthalmology Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Department of Ophthalmology Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oshima
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.affiliation: Department of Ophthalmology Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D006801:Humans; D007231:Infant, Newborn; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000633:toxicity; D012313:RNA / Q000235:genetics; D015861:Retinal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D012178:Retinopathy of Prematurity / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D012313:RNA; D010100:Oxygen