title: Suppression of experimental choroidal neovascularization by curcumin in mice.
abstract: OBJECTIVE
  To investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms.
  
  
  METHODS
  C57BL/6N mice were pretreated with intraperitoneal injections of curcumin daily for 3 days prior to laser-induced CNV, and the drug treatments were continued until the end of the study. The CNV area was analyzed by fluorescein-labeled dextran angiography of retinal pigment epithelium (RPE)-choroid flat mounts on day 7 and 14, and CNV leakage was evaluated by fluorescein angiography (FA) on day 14 after laser photocoagulation. The infiltration of F4/80 positive macrophages and GR-1 positive granulocytes were evaluated by immunohistochemistry on RPE-choroid flat mounts on day 3. Their expression in RPE-choroid complex was quantified by real-time PCR (F4/80) and Western blotting (GR-1) on day 3. RPE-choroid levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 were examined by ELISA on day 3. Double immunostaining of F4/80 and VEGF was performed on cryo-sections of CNV lesions on day 3. The expression of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)-1α in the RPE-choroid was determined by Western blotting.
  
  
  RESULTS
  Curcumin-treated mice had significantly less CNV area (P<0.05) and CNV leakage (P<0.001) than vehicle-treated mice. Curcumin treatment led to significant inhibition of F4/80 positive macrophages (P<0.05) and GR-1 positive granulocytes infiltration (P<0.05). VEGF mainly expressed in F4/80 positive macrophages in laser injury sites, which was suppressed by curcumin treatment (P<0.01). Curcumin inhibited the RPE-choroid levels of TNF-α (P<0.05), MCP-1 (P<0.05) and ICAM-1 (P<0.05), and suppressed the activation of NF-κB in nuclear extracts (P<0.05) and the activation of HIF-1α (P<0.05).
  
  
  CONCLUSIONS
  Curcumin treatment led to the suppression of CNV development together with inflammatory and angiogenic processes including NF-κB and HIF-1α activation, the up-regulation of inflammatory and angiogenic cytokines, and infiltrating macrophages and granulocytes. This provides molecular and cellular evidence of the validity of curcumin supplementation as a therapeutic strategy for the suppression of age-related macular degeneration (AMD)-associated CNV.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.forename: WeiWei
authors.initials: W
authors.lastname: Zhang
authors.forename: Songtao
authors.initials: S
authors.lastname: Yuan
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Chen
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.forename: DongQing
authors.initials: D
authors.lastname: Yuan
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: QingHuai
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005451:Fluorescein Angiography; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003474:Curcumin