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H. Zhang, G. Duncan, L. Wang, P. Liu, H. Cui; Mechanism of Action of Arsenic Trioxide on Human Lens Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4229.
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Arsenic compounds have been used in the treatment of different cancers and recently Arsenic trioxide (As2O3) has been approved by the FDA for the treatment of acute promyelocytic leukemia. This was therefore a promising compound to test for PCO inhibition.
As2O3 was dissolved and then diluted in EMEM and added to FHL124 cultured cells and capsular bags. Cell growth was monitored by Coomassie Blue staining and by phase microscopy. At the end of the culture period, cells were collected for RT-PCR and real-time PCR (Taqman) and protein analyses (Western Blot) . As2O3-induced changes in cell calcium were determined by real-time imaging techniques after Fura-2 incorporation.
As2O3 inhibited the growth of FHL 124 cells in a dose-dependent manner in the range 1uM-100µm. Exposure of FHL124 cells to As2O3 in this range led to store depletion, blockage of calcium entry and eventually total inhibition of calcium signalling. There was a concomitant upregulation of the ER stress genes: EIF2α, IRE1 and ATF6. The calcium binding protein calcineurin -PPP3CA was also upregulated. There was an over expression of the ER chaperone Bip and the crystallin chaperone αAB crystallin. There was also upregulation of the active-apoptotic caspase3. A higher concentration 1mM was required to inhibit cell growth across the posterior surface of the capsular bag. However, using the perfect capsule system, the compound was also effective in inhibiting cell growth after only a two-minute application.
Arsenic trioxide is effective in reducing PCO as it induces apopotosis through an ER stress mechanism: It shows considerable promise as a PCO-reducing agent.
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