Effect of thiazolidinedione on the proliferation of bovine retinal endothelial cells stimulated by vascular endothelial cell growth factor

Purpose: To investigate the effect of troglitazone, an antidiabetic drug, on the cytosolic Ca²⁺ concentrations ([Ca²⁺]i) and the cell cycles of bovine retinal endothelial cells (RECs) stimulated with vascular endothelial growth factor (VEGF). Methods: The changes in [Ca²⁺]i were monitored using microfluorometry with Fura-2. The phase of the cell cycle was examined by an immunocytochemical analysis using monoclonal antibodies against cell cycle-specific nuclear antigens. Results: In the presence of extracellular Ca²⁺, VEGF-induced transient [Ca²⁺]i elevation followed by continuous steady-state elevation resulted in cell cycle progression in RECs. The removal of extracellular Ca²⁺ inhibited the continuous component, but transient [Ca²⁺]i elevation was still observed. These results are compatible with the hypothesis that a continuous steady-state elevation of [Ca²⁺]i may be mediated mainly through the influx of extracellular Ca²⁺. Pretreatment with 10 μM troglitazone prevented the transient and continuous steady-state elevation of [Ca ²⁺]i, resulting in an inhibition of the cell cycle in RECs stimulated with VEGF. Conclusions: These data suggest that troglitazone inhibits VEGF-induced cell cycle progression through the inhibition of [Ca²⁺]i in RECs.