Inhibition of laser-induced choroidal neovascularization by atorvastatin by downregulation of monocyte chemotactic protein-1 synthesis in mice

Abstract

Purpose: To determine the effect of atorvastatin, an HMG CoA reductase inhibitor, on experimental choroidal neovascularization (CNV) induced by laser photocoagulation in mice.

Methods: 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.

Results: 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.

Conclusions: 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.