Carboxyamido-triazole modulates retinal pigment epithelial and choroidal endothelial cell attachment, migration, proliferation, and MMP-2 secretion of choroidal endothelial cells.

Stephan Hoffmann, Shikun He, Man Lin Jin, Laura Masiero, Peter Wiedemann, Stephen J Ryan, Elise C Kohn

Index: Curr. Eye Res. 30(2) , 103-13, (2005)

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Abstract

To determine the effect of the calcium signaling modulating drug carboxyamido-triazole (CAI) on substeps of exudative age-related macular degeneration (AMD) in vitro.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 microg/ml) with and without CAI (0.1-10 microM) was measured by cell counting and 3H-uptake. Viability and apoptosis of the exposed cells was assessed by an MTT and an apoptosis assay.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 microM CAI). CAI reduced the cellular viability by apoptosis induction.CAI inhibits substeps of exudative macular degeneration and may be of value for the treatment of the disease.