Abstract
Abstract Purpose The aim of the present study was to examine the effect of the sigma‐2 receptor agonist, Siramesine, on morphology, growth, cell death, lysosomal function and effects on extra‐lysosomal proteolytic systems in human lens epithelial cells. Methods Human lens epithelial cells in culture were exposed to siramesine and examined for morphological changes using Nomarski optics or calcein. Lysosomes were evaluated using acridine orange and MagicRed. Nuclear morphology was studied using Hoechst 33342 and propidium iodide. Enzymatic activities in living cells or cell lysates were studied using different fluorogenic substrates. Results Siramesine at low concentrations increased the cytoplasmic proteolytic activity of the proteasome and the calpain system. 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 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.
Published Version
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