Inhibition of Choroidal Neovascularization With an Anti-Inflammatory Carotenoid Astaxanthin

Abstract

Purpose: : Astaxanthin (AST) is a carotenoid found in marine animals and vegetables. The aim 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 an intraperitoneal injection of AST daily for 3 days before photocoagulation and the treatment were continued daily till the end of the study. CNV response was analyzed by volumetric measurements 1 week after laser injury. Retinal pigment epithelium (RPE)-choroidal levels of IΚB-α, intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, vascular endothelial growth factor (VEGF), VEGF receptor-1 (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-ΚB and the expression of inflammatory molecules.

Results: : The index of CNV volume was significantly suppressed by the treatment with AST, compared with 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-ΚB pathway including IΚB-α degradation and p65 nuclear translocation.

Conclusions: : AST treatment led to significant suppression of CNV development together with inflammatory processes including NF-ΚB activation, subsequent upregulation of inflammatory molecules and macrophage infiltration. The present study suggests the possibility of AST supplementation as a therapeutic strategy to suppress CNV associated with AMD.

Keywords: age-related macular degeneration • choroid: neovascularization • carotenoids/carotenoid binding proteins