Abstract: To investigate the effects of the unfolded protein response(UPR) in endoplasmic reticulum stress on apoptosis of human lens epithelial cells (hLECs) and the relationship between UPR and cataract formation. MethodsCultured hLECs were divided into the control group and stimulated groups A, B, C and D, which were cultured in 1640 with homocysteine(1, 2, 5 and 10mmol／L) for 24h. Inhibition of the cell proliferation was determined by MTT assay; cell apoptosis was determined by Hoechst staining; free glutathione was determined using a Glutathione Quantigication Kit; the levels of cytosolic ROS were determined by adding H2DCFHDA for 20 to 30min followed by imaging with a fluorescent microscope; and the expressions of Bip／GRP78 and Caspase12 in stimulated cells were determined by Western blot. ResultsAfter being exposed to different concentrations of Hcy, LECs showed a dosedependent decrease in cell vitality: 48.2％ declined at 5mmol／L concentration of Hcy and 57.7％ declined at 10mmol／L concentration of Hcy, which showed significant differences compared with the control group (P<001). Also significant apoptotic cells were determined. Compared with the control group, the level of ROS increased in a dosedependent manner and of GSH was decreased in the C and D groups(P<0.05), also the expressions of GRP78 and Caspase-12 were significantly increased in the C and D groups (P<0.05). ConclusionsHigh concentration of endoplasmic reticulum stressors can induce the endoplasmic reticulum and induce apoptosis of LECs through UPR. The conclusion can be drawn that UPR is probably one of the initiating factors of cataracts.

Key words: Cataract, Pathogenesis, Endoplasmic reticulum, Unfolded protein response, Apoptosis