Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin

Kanako Izumi-Nagai, Norihiro Nagai, Kazuhiro Ohgami, Shingo Satofuka, Yoko Ozawa, Kazuo Tsubota, Shigeaki Ohno, Yuichi Oike, Susumu Ishida

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Abstract

Purpose. 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 IkB-α, 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-kB 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-kB pathway, including IkB-α degradation and p65 nuclear translocation. Conclusions. AST treatment, together with inflammatory processes including NF-kB 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.

Original languageEnglish
Pages (from-to)1679-1685
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number4
DOIs
Publication statusPublished - 2008 Apr

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Izumi-Nagai, K., Nagai, N., Ohgami, K., Satofuka, S., Ozawa, Y., Tsubota, K., Ohno, S., Oike, Y., & Ishida, S. (2008). Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin. Investigative Ophthalmology and Visual Science, 49(4), 1679-1685. https://doi.org/10.1167/iovs.07-1426