Inhibition of Laser-Induced Choroidal Neovascularization by Atorvastatin by Downregulation of Monocyte Chemotactic Protein-1 Synthesis in Mice

Abstract

To determine the effect of atorvastatin, an HMG CoA reductase inhibitor, on experimental choroidal neovascularization (CNV) induced by laser photocoagulation in mice. CNV was induced by laser photocoagulation in normal wild-type mice. The mice received either oral atorvastatin 10 (AS10 group) or 20 (AS20 group) mg/kg per day 3 days before and after laser application; 1 (AS1) and 2 (AS2) mg/kg per day were included in the measurement of the parameters of CNV volume and the expression of chemoattractant CC chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) and intracellular adhesion molecule (ICAM)-1. CNV responses were compared based on volume measurements 2 weeks after laser photocoagulation. Expression of vascular endothelial growth factor (VEGF), CCL2/MCP-1, and ICAM-1 in the RPE and choroid was quantified by ELISA 2 or 3 days after photocoagulation. Macrophage infiltration of the choroid was determined by flow cytometry. The mean CNV volume was significantly smaller in the AS1 (44.16 +/- 4.67 x 10(4) microm(3)), AS2 (36.49 +/- 4.64 x 10(4) microm(3)), AS10 (25.75 +/- 2.41 x 10(4) microm(3)), and AS20 (33.24 +/- 8.42 x 10(4) microm(3)) groups compared with control mice (64.21 +/- 2.27 x 10(4) microm(3); P = 0.0004, P < 0.0001, P < 0.0001, P < 0.0001, respectively). The mean VEGF and CCL2/MCP-1 protein levels decreased significantly (P = 0.001, P = 0.02, respectively) in the treated group compared with the control group. ICAM-1 expression did not differ significantly between the treated and control groups. The number of choroid-infiltrating macrophages decreased markedly in the treated group. Atorvastatin effectively inhibited laser-induced CNV in mice and was associated with downregulation of CCL2/MCP-1 and VEGF and reduced macrophage infiltration into the RPE/choroid.