BACKGROUND: Retinal pigment epithelial cells (RPE cells) and choroidal endothelial cells (CECs) are important cell types in the process of choroidal neovascularization in exudative age-related macular degeneration (AMD). In this study, we evaluated the antiproliferative and antimigratory abilities of carboxyamido-triazole (CAI), a drug modulating calcium-dependent signal transduction on RPE cells and CECs. METHODS: Human fetal RPE cells and bovine CECs were exposed to CAI in a concentration range of 0.1 to 10 microM. Cell proliferation was stimulated with 10% serum or 10 ng/ml bFGF. The effect of CAIs on cell proliferation was estimated. Furthermore, we evaluated CAI's effects on CEC and RPE cell migration induced by fibronectin. RESULTS: CAI had a stronger inhibitory effect on serum-induced CEC proliferation than on RPE cell proliferation. A much stronger effect was seen on the proliferation of bFGF-stimulated RPE cells and CECs. Furthermore, the fibronectin-stimulated migration of RPE cells and CECs was inhibited by CAI. In this assay, a stronger inhibitory effect was seen on RPE cells than on CECs. CONCLUSION; CAI inhibits important substeps of choroidal neovascularization on RPR cells and CECs. Therefore, CAI may be of value for the treatment of choroidal neovascularization in exudative AMD.
BACKGROUND: Retinal pigment epithelial cells (RPE cells) and choroidal endothelial cells (CECs) are important cell types in the process of choroidal neovascularization in exudative age-related macular degeneration (AMD). In this study, we evaluated the antiproliferative and antimigratory abilities of carboxyamido-triazole (CAI), a drug modulating calcium-dependent signal transduction on RPE cells and CECs. METHODS:Human fetal RPE cells and bovine CECs were exposed to CAI in a concentration range of 0.1 to 10 microM. Cell proliferation was stimulated with 10% serum or 10 ng/ml bFGF. The effect of CAIs on cell proliferation was estimated. Furthermore, we evaluated CAI's effects on CEC and RPE cell migration induced by fibronectin. RESULTS:CAI had a stronger inhibitory effect on serum-induced CEC proliferation than on RPE cell proliferation. A much stronger effect was seen on the proliferation of bFGF-stimulated RPE cells and CECs. Furthermore, the fibronectin-stimulated migration of RPE cells and CECs was inhibited by CAI. In this assay, a stronger inhibitory effect was seen on RPE cells than on CECs. CONCLUSION; CAI inhibits important substeps of choroidal neovascularization on RPR cells and CECs. Therefore, CAI may be of value for the treatment of choroidal neovascularization in exudative AMD.
Authors: E C Kohn; E Reed; G Sarosy; M Christian; C J Link; K Cole; W D Figg; P A Davis; J Jacob; B Goldspiel; L A Liotta Journal: Cancer Res Date: 1996-02-01 Impact factor: 12.701