As molecular mechanisms for suppressing CNV, the present data showed the AST-induced suppression of various inflammation-related molecules, including VEGF, VEGFR-1, VEGFR-2, IL-6, ICAM-1, and MCP-1, which were upregulated after the induction of CNV
(Fig. 3) . Previous reports concerning the molecular mechanisms underlying CNV generation showed VEGF as a promoting mediator.
5 31 34 Macrophages infiltrating into CNV are a rich source of VEGF. VEGFR-1 is expressed in inflammatory leukocytes, including macrophages.
35 The AST-induced decrease in RPE–choroid VEGF and VEGFR-1, seen in the present study
(Fig. 3) , is compatible with and is explained at least in part by the suppression of VEGF-secreting and VEGFR-1-bearing macrophage infiltration. Indeed, our in vitro experiments
(Fig. 4)showed no remarkable effects on VEGF production either in macrophages or in RPE cells after AST treatment (data not shown). Additionally, we performed in vitro experiments showing that IL-6 levels in macrophages, MCP-1 levels in RPE cells, and ICAM-1, MCP-1, and VEGFR-2 levels in vascular endothelial cells were significantly reduced by AST
(Fig. 4) . Recently, we have shown that CNV formation is mediated by IL-6 receptor signaling.
14 Several in vivo experiments with genetically altered mice demonstrated a significant contribution of adhesion molecules and chemotactic factors, including ICAM-1
10 and MCP-1,
36 both of which are required for macrophage infiltration. VEGF-mediated endothelial cell mitogenic activity was shown to depend on VEGFR-2.
37 Collectively, the presently observed suppression of CNV by treatment with AST is likely attributable to the inhibition of multiple inflammatory steps, including MCP-1–induced migration and ICAM-1-dependent adhesion of macrophages, subsequent macrophage-derived VEGF and IL-6 secretion, and VEGFR-2 expression in endothelial cells.