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Suppression of experimental choroidal neovascularization by curcumin in mice.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (12), pp. e53329. Date of Electronic Publication: 2012 Dec 28. - Publication Year :
- 2012
-
Abstract
- Purpose: To investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms.<br />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.<br />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).<br />Conclusion: 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.
- Subjects :
- Animals
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Anti-Inflammatory Agents, Non-Steroidal therapeutic use
Choroidal Neovascularization diagnosis
Choroidal Neovascularization drug therapy
Choroidal Neovascularization pathology
Curcumin pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Fluorescein Angiography
Granulocytes drug effects
Granulocytes physiology
Macrophages drug effects
Macrophages physiology
Male
Mice
Mice, Inbred C57BL
Choroidal Neovascularization prevention & control
Curcumin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23285282
- Full Text :
- https://doi.org/10.1371/journal.pone.0053329