Inhibitory effects of verapamil isomers on the proliferation of choroidal endothelial cells

Abstract

To evaluate the effects of verapamil isomers on in vitro proliferation of bovine choroidal endothelial cells (CECs). CECs were isolated from bovine eyes and cultured in endothelial growth medium (EGM). For the proliferation assays, CECs were exposed to verapamil isomers (0.1-100 microM) in EGM with 2% fetal bovine serum or basic fibroblast growth factor (bFGF) (10 ng/ml). After 72 h of incubation with the desired drug, the cellular proliferation was determined by an MTT assay and a BrdU assay. In addition, the drug toxicity on CECs stimulated with EGM was evaluated by cell counting with trypan blue. All verapamil isomers inhibited the bFGF- or medium-stimulated growth significantly in a concentration range of 10-40 microM without toxicity. No significant differences were seen between the inhibitory effects of the various isomers. Cell toxicity was detected at a concentration of 100 microM verapamil isomers on EGM-stimulated CECs. The results demonstrate the efficacy of all verapamil isomers in inhibiting CEC proliferation involved in the process of choroidal neovascularization. D: -(+)-Verapamil may be recommended for further in vivo evaluation in an animal model of exudative AMD; it has fewer systemic and local side effects because calcium channels are not blocked.