Alterations of Calcium Homeostasis Affect the Survival of Human Retinal Epithelial Cells

Abstract

1. This study demonstrated that the modification of calcium concentrations ([Ca2 +]) could severely affect the viability of human retinal pigment epithelial (ARPE19) cells. 2. Pharmacological agents with varying mechanisms of action: verapamil (VP), diltiazem (DIL), caffeine (CF), papaverine (PA), forskolin (FSK), ryanodine (RYN), thapsigargin (THG), and cyclosporin A (CysA) were used to evaluate the effect of modifying cytosolic Ca2 + on the viability of ARPE19 cells. The difference in cell proliferations under different treatments was performed using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Ca2 +‐imaging was used to determine the changes in intracellular Ca2 + levels ([Ca2 +]i) over 5 min of drug treatments. 3. Amongst the agents tested, PA, RYN, and THG actually increased the total number of cells initially on Day 1. However, apart from PA, all caused significant reduction of cell viability by Day 5. Variable [Ca2 +]i levels in the cells were obtained with significant rises in the presence of DIL, CF, PA, FSK, and CysA. Verapamil, RYN, and THG caused a rise in [Ca2 +]i, but the effect was not significant. 4. The present study showed that the APRE19 cells were very sensitive to the Ca2 + homeostasis. It is possible that other ocular cells may also display such vulnerability. Therefore, clinically used pharmacological agents that are known to affect Ca2 + must be treated with caution.