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

Curr Eye Res. 2005 Feb;30(2):103-13. doi: 10.1080/02713680490894595.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Calcium Channel Blockers / pharmacology*
  • Cattle
  • Cell Adhesion / drug effects
  • Cell Count
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Choroid / blood supply
  • Collagen Type IV / metabolism
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / enzymology
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibronectins / metabolism
  • Humans
  • Laminin / metabolism
  • Matrix Metalloproteinase 2 / metabolism*
  • Pigment Epithelium of Eye / cytology*
  • Pigment Epithelium of Eye / metabolism
  • Triazoles / pharmacology*
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Calcium Channel Blockers
  • Collagen Type IV
  • Fibronectins
  • Laminin
  • Triazoles
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • carboxyamido-triazole
  • Matrix Metalloproteinase 2