title: Suppression of Retinal Neovascularization by Anti-CCR3 Treatment in an Oxygen-Induced Retinopathy Model in Mice.
abstract: OBJECTIVE
  To investigate the association between retinal neovascularization and the CC chemokine receptor-3 (CCR3) in a mouse model of oxygen-induced retinopathy (OIR).
  
  
  METHODS
  An OIR model in C57BL/6J mice was used as a retinal neovascularization model. An enzyme-linked immunosorbent assay was performed to evaluate the chronological change in vascular endothelial growth factor A (VEGF-A) and eotaxin expressions. CCR3 and VEGF subtype expression in the retina was examined using real-time RT-PCR, and CCR3, eotaxin, VEGF-A, and CD31 expression was examined immunohistochemically. A CCR3 neutralizing antibody (Ab) was injected into the vitreous humor on both postnatal days 12 (P12) and 14 (P14). Retinal neovascularizations were quantified by measurement of the percentages of neovascular area.
  
  
  RESULTS
  The mean eotaxin and VEGF-A protein level was significantly downregulated at P10 and P12 and was significantly upregulated at P14 and P17 (p < 0.05). CCR3 mRNA expression was significantly upregulated at P12 (p < 0.05). VEGF164 mRNA expression was significantly upregulated at P14 (p < 0.05). The areas of vaso-obliteration and neovascularization were significantly suppressed in anti-CCR3 Ab-treated eyes (p < 0.05). Anti-CCR3 Ab treatment suppressed VEGF and eotaxin but not monocyte chemoattractant protein-1. And VEGF 164 mRNA but not VEGF120 mRNA was suppressed by anti-CCR3 Ab treatment.
  
  
  CONCLUSIONS
  The present data suggest that anti-CCR3 treatment can suppress retinal neovascularization. Anti-CCR3 treatment may have potential as a new therapy for retinopathies with retinal neovascularization such as diabetic retinopathy and retinopathy of prematurity.
authors.affiliation: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Hirahara
authors.forename: Miho
authors.initials: M
authors.lastname: Nozaki
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ohbayashi
authors.forename: Norio
authors.initials: N
authors.lastname: Hasegawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ozone
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ogura
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000633:toxicity; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors*; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; C515351:Ccr3 protein, mouse; D016207:Cytokines; D054397:Receptors, CCR3; D010100:Oxygen
keywords: CCR3; Eotaxin; Oxygen-induced retinopathy; Retinal neovascularization; Vascular endothelial growth factor