title: Angiostatic effect of CXCR3 expressed on choroidal neovascularization.
abstract: OBJECTIVE
  Several recent studies suggest that some chemokines/chemokine receptors are involved in choroidal neovascularization (CNV). CXCR3 was the focus of the present study because microarray analysis for murine laser-induced CNV model showed the increased expression of CXCR3. The purpose of this study was to evaluate the effect of CXCR3 on CNV.
  
  
  METHODS
  Microarray analysis was performed for the mouse eyes with laser-induced CNV. CXCR3 expressions on the CNV were evaluated by immunohistochemistry and real-time RT-PCR. CNV was compared between CXCR3-deficient mice and wild-type mice, between mice treated with anti-CXCR3/anti-IP-10 neutralizing antibody and mice treated with control IgG. Macrophage recruitment into CNV was also investigated. Ocular expressions of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), C-C chemokine ligand-2 (CCL2), and complement component-3 (C3) were evaluated by real-time PCR.
  
  
  RESULTS
  Microarray analysis and real-time RT-PCR revealed the elevation of CXCR3 and IP-10 in laser-treated mouse eyes compared with control eyes. Immunohistochemistry showed CXCR3 expression on the endothelial cells of CNV. Laser-induced CNV of CXCR3-deficient mice was significantly larger, with greater leakage in fluorescein angiography, and with greater macrophage-infiltration compared with wild-type mice (P < 0.01). Intravitreal injection of anti-CXCR3/anti-IP-10 neutralizing antibody exacerbated CNV. The CCL2 expression in the laser-treated eyes of CXCR3-deficient mice was higher than in those of wild-type mice (P < 0.05), whereas VEGF, PEDF, and C3 showed no differences.
  
  
  CONCLUSIONS
  These results suggested that CXCR3 expressed on CNV could have an angiostatic effect on it.
authors.affiliation: Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Fujimura
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yuda
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueta
authors.forename: Aya
authors.initials: A
authors.lastname: Iriyama
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Inoue
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Kaburaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yanagi
mesh_terms: D000818:Animals; D002829:Choroid / Q000378:metabolism / Q000473:pathology; D020256:Choroidal Neovascularization / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics*; D054367:Receptors, CXCR3 / Q000096:biosynthesis / Q000235:genetics*; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C515188:Cxcr3 protein, mouse; D012333:RNA, Messenger; D054367:Receptors, CXCR3