title: Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin.
abstract: OBJECTIVE
  Astaxanthin (AST) is a carotenoid found in marine animals and vegetables. The purpose of the present study was to investigate the effect of AST on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms.
  
  
  METHODS
  Laser photocoagulation was used to induce CNV in C57BL/6J mice. Mice were pretreated with intraperitoneal injections of AST daily for 3 days before photocoagulation, and treatments were continued daily until the end of the study. CNV response was analyzed by volumetric measurements 1 week after laser injury. Retinal pigment epithelium-choroid levels of IkappaB-alpha, intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1, and VEGFR-2 were examined by Western blotting or ELISA. AST was applied to capillary endothelial (b-End3) cells, macrophages, and RPE cells to analyze the activation of NF-kappaB and the expression of inflammatory molecules.
  
  
  RESULTS
  The index of CNV volume was significantly suppressed by treatment with AST compared with that in vehicle-treated animals. AST treatment led to significant inhibition of macrophage infiltration into CNV and of the in vivo and in vitro expression of inflammation-related molecules, including VEGF, IL-6, ICAM-1, MCP-1, VEGFR-1, and VEGFR-2. Importantly, AST suppressed the activation of the NF-kappaB pathway, including IkappaB-alpha degradation and p65 nuclear translocation.
  
  
  CONCLUSIONS
  AST treatment, together with inflammatory processes including NF-kappaB activation, subsequent upregulation of inflammatory molecules, and macrophage infiltration, led to significant suppression of CNV development. The present study suggests the possibility of AST supplementation as a therapeutic strategy to suppress CNV associated with AMD.
authors.affiliation: Laboratory of Retinal Cell Biology, Keio University of Medicne, Tokyo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Izumi-Nagai
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nagai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ohgami
authors.forename: Shingo
authors.initials: S
authors.lastname: Satofuka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism; D002829:Choroid / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D020672:I-kappa B Proteins / Q000378:metabolism; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D024341:Xanthophylls / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; C090509:Icam1 protein, mouse; D015850:Interleukin-6; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D042461:Vascular Endothelial Growth Factor A; D024341:Xanthophylls; C467480:vascular endothelial growth factor A, mouse; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; C005948:astaxanthine; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2