Carboxyamido-triazole modulates retinal pigment epithelial and choroidal endothelial cell attachment, migration, proliferation, and MMP-2 secretion of choroidal endothelial cells.
OBJECTIVE
To determine the effect of the calcium signaling modulating drug carboxyamido-triazole (CAI) on substeps of exudative age-related macular degeneration (AMD) in vitro.


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 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.


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 microM 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.
Hoffmann
Stephan
S
Department of Ophthalmology, University of Leipzig, Leipzig, Germany. HoffmS@web.de
He
Shikun
S
Jin
Man Lin
ML
Masiero
Laura
L
Wiedemann
Peter
P
Ryan
Stephen J
SJ
Kohn
Elise C
EC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002829:Choroid / Q000098:blood supply; D024141:Collagen Type IV / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000201:enzymology; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000166:cytology* / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D002121:Calcium Channel Blockers; D024141:Collagen Type IV; D005353:Fibronectins; D007797:Laminin; D014230:Triazoles; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C062058:carboxyamido-triazole; D020778:Matrix Metalloproteinase 2