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X Wang, Z Guo, JW Simpkins, PR Cammarata; Protective Effect of Estrogen Against Oxidative Damage in Cultured Human Lens Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):849.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Epidemiological studies identify a higher rate of occurrence of cataracts in estrogen-deficient postmenopausal women but the mechanism for this increased risk is ambiguous. Elevated level of H2O2 in lens epithelium has been associated with cataractogenesis. Therefore, one explanation for the increased incidence of cataract in these women might be a reduced capacity to cope with oxidative stress. In the study presented herein, we tested, for the first time, the protective effect of estrogen against oxidative stress using in vitro cultured human lens epithelial cells (HLECs). Methods: To address the involvement of 17ß-Estradiol (17ß-E2) protection against oxidative stress, HLECs were exposed to H2O2 insult at physiological level (100 µM) over a time-course of several hours with and without pretreatment of 17ß-E2. Cell viability was measured by Calcein AM assay and 2,7-dichlorofluorescin diacetate (DCFH-DA) was used to determine intracellular reactive oxygen species (ROS). Intracellular ATP level was quantified using a luciferin and luciferase-based assay. Results: H2O2 caused a significant decrease in cell viability and intracellular ATP level; a dose dependent increase in both cell viability and intracellular ATP level was observed with a 2 hour 17ß-E2 pretreatment prior to oxidative insult. At 1 nM, 17ß-E2 increased the cell viability from 39.0 3.65 % to 75.1 2.6 % while at 100 nM or higher, 17ß-E2 raised the survival percentage to greater than 95%. Intracellular ATP level approached normal with 17ß-E2 at 100 nM or higher. 17ß-E2 did not abate intracellular ROS accumulation as prompted by H2O2 exposure. Furthermore, two non-feminizing estrogens, 17α-E2 and ent-E2, both of which lack binding to either estrogen receptor α or ß, were as effective as 17ß-E2 in cell viability recovery. Conclusion: The present study indicates that 17ß-E2 can preserve cell viability and ATP level opposing oxidative stress. While the precise mode of protection of 17ß-E2 against oxidative stress remains to be determined, the ability of non-feminizing estrogens to protect against the toxicity of intracellular H2O2 accumulation indicates that this preservation may not be mediated through classical estrogen receptors.
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