Abstract
Abstract Purpose The aim was to investigate the mechanisms of cell death in lens epithelial cells after administration of siramesine, a sigma‐2 receptor agonist. Methods Human lens epithelial cells in culture were exposed to siramesine and examined for morphological changes using DIC or calcein as a cytoplasmic marker. Lysosomes were studied using acridine orange and MagicRed. Proteolytic activity of the proteasome, calpain, caspases and cathepsins in living cells or cell extracts were studied using different fluorogenic substrates. Results Siramesine at low concentrations increased the cytoplasmic proteolytic activity of the proteasome and the calpain system. Early effects was also observed with respect to lysosomal morphology, acidity and function. Activation of caspase‐3 and the appearance of nuclei with an apoptotic morphology were also found. Conclusion Siramesine at very low concentrations affects lens epithelial cells with perturbation of the major proteolytic systems, lysosomal morphology and results in caspase activation and cell death. Siramesine may be a promising substance for clinical studies concerning the treatment of PCO.
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