Carboxyamido-Triazole Modulates Retinal Pigment Epithelial and Choroidal Endothelial Cell Attachment, Migration, Proliferation, and MMP-2 Secretion of Choroidal Endothelial Cells

Abstract

Purpose: To determine the effect of the calcium signaling modulating drug carboxyamido-triazole (CAI) on substeps of exudative age-related macular degeneration (AMD) in vitro. Materials and Methods: Zymography and ELISA determined the effect of CAI on MMP-2 production of choroidal endothelial cells (CECs) stimulated by bFGF and VEGF. The effects of CAI on attachment of retinal pigment endothelial (RPE) cells/CECs onto fibronectin, laminin, collagen IV, and migration toward fibronectin were investigated. Proliferation induced by serum and bFGF (10 μ g/ml) with and without CAI (0.1–10 μ M) was measured by cell counting and H-uptake. Viability and apoptosis of the exposed cells was assessed by an MTT and an apoptosis assay. Results: CAI inhibited serum- and bFGF-induced proliferation, cell attachment onto fibronectin and collagen IV, but only CEC attachment onto laminin. Inhibition of MMP-2 production was observed (10 μ M CAI). CAI reduced the cellular viability by apoptosis induction. Conclusions: CAI inhibits substeps of exudative macular degeneration and may be of value for the treatment of the disease.

KEYWORDS:

• age-related macular degeneration;
• choroidal endothelial cell;
• choroidal neovascularization;
• retinal pigment epithelial cell;
• signal transduction therapy