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Sigma‐2 receptor agonists kill lens epithelial cells
Author(s) -
KARLSSON JO,
JONHEDE S,
PETERSEN A,
ZETTERBERG M
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2010.3344.x
Subject(s) - acridine orange , propidium iodide , microbiology and biotechnology , apoptosis , biology , lysosome , trypan blue , cell culture , calpain , programmed cell death , chemistry , biochemistry , enzyme , genetics
Purpose The aim of the present study was to examine the effects 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. In addition we compared the effects to that obtained in other human cells in primary culture. 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 Magic Red (RR‐cresyl violet). Nuclear morphology was studied using Hoechst 33342 and propidium iodide. Enzymatic activities in living cells or cell lysates were studied using fluorogenic substrates. Results Siramesine at low concentrations increased the cytoplasmic proteolytic activity of the proteasome and the calpain system. Effects were also observed with respect to lysosomal morphology, acidity and function. In addition, activation of caspase‐3 and the appearance of nuclei with an apoptotic morphology was found. Lens epithelial cells appeared to be more sensitive to siramesine than other cells. Conclusion Siramesine at low concentrations affects lens epithelial cells with perturbations of the major proteolytic systems and lysosomal morphology, resulting in caspase activation and cell death. Siramesine may be a possible substance for the treatment or prevention of posterior capsular opacification (PCO).