Cargando…

Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice

PURPOSE: 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...

Descripción completa

Detalles Bibliográficos
Autores principales: Xie, Ping, Zhang, WeiWei, Yuan, Songtao, Chen, Zhiqiang, Yang, Qin, Yuan, DongQing, Wang, Feng, Liu, QingHuai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532428/
https://www.ncbi.nlm.nih.gov/pubmed/23285282
http://dx.doi.org/10.1371/journal.pone.0053329
_version_ 1782254311337623552
author Xie, Ping
Zhang, WeiWei
Yuan, Songtao
Chen, Zhiqiang
Yang, Qin
Yuan, DongQing
Wang, Feng
Liu, QingHuai
author_facet Xie, Ping
Zhang, WeiWei
Yuan, Songtao
Chen, Zhiqiang
Yang, Qin
Yuan, DongQing
Wang, Feng
Liu, QingHuai
author_sort Xie, Ping
collection PubMed
description PURPOSE: 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). 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.
format Online
Article
Text
id pubmed-3532428
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-35324282013-01-02 Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice Xie, Ping Zhang, WeiWei Yuan, Songtao Chen, Zhiqiang Yang, Qin Yuan, DongQing Wang, Feng Liu, QingHuai PLoS One Research Article PURPOSE: 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). 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. Public Library of Science 2012-12-28 /pmc/articles/PMC3532428/ /pubmed/23285282 http://dx.doi.org/10.1371/journal.pone.0053329 Text en © 2012 Xie et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Xie, Ping
Zhang, WeiWei
Yuan, Songtao
Chen, Zhiqiang
Yang, Qin
Yuan, DongQing
Wang, Feng
Liu, QingHuai
Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice
title Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice
title_full Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice
title_fullStr Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice
title_full_unstemmed Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice
title_short Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice
title_sort suppression of experimental choroidal neovascularization by curcumin in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532428/
https://www.ncbi.nlm.nih.gov/pubmed/23285282
http://dx.doi.org/10.1371/journal.pone.0053329
work_keys_str_mv AT xieping suppressionofexperimentalchoroidalneovascularizationbycurcumininmice
AT zhangweiwei suppressionofexperimentalchoroidalneovascularizationbycurcumininmice
AT yuansongtao suppressionofexperimentalchoroidalneovascularizationbycurcumininmice
AT chenzhiqiang suppressionofexperimentalchoroidalneovascularizationbycurcumininmice
AT yangqin suppressionofexperimentalchoroidalneovascularizationbycurcumininmice
AT yuandongqing suppressionofexperimentalchoroidalneovascularizationbycurcumininmice
AT wangfeng suppressionofexperimentalchoroidalneovascularizationbycurcumininmice
AT liuqinghuai suppressionofexperimentalchoroidalneovascularizationbycurcumininmice