Selective effects of estradiol on human corneal endothelial cells.
Selective effects of estradiol on human corneal endothelial cells.
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雌二醇对人角膜内皮细胞的选择性作用。
DOI:
10.1101/2023.04.27.538629
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发表时间:
2023
期刊:
影响因子:
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通讯作者:
Patel,SangitaP
中科院分区:
文献类型:
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作者:
Han,Seoyoung;Mueller,Christian;Wuebbolt,Caitlin;Kilcullen,Sean;Nayyar,Varinda;Gonzalez,BrayanCalle;Fard,AliMahdavi;Floss,JamieC;Morales,MichaelJ;Patel,SangitaP
In Fuchs endothelial corneal dystrophy (FECD), mitochondrial and oxidative stresses in corneal endothelial cells (HCEnCs) contribute to cell demise and disease progression. FECD is more common in women than men, but the basis for this observation is poorly understood. To understand the sex disparity in FECD prevalence, we studied the effects of the sex hormone 17-β estradiol (E2) on growth, oxidative stress, and metabolism in primary cultures of HCEnCs grown under physiologic ([O2]2.5) and hyperoxic ([O2]A) conditions. We hypothesized that E2 would counter the damage of oxidative stress generated at [O2]A. HCEnCs were treated with or without E2 (10 nM) for 7–10 days under both conditions. Treatment with E2 did not significantly alter HCEnC density, viability, ROS levels, oxidative DNA damage, oxygen consumption rates, or extracellular acidification rates in either condition. E2 disrupted mitochondrial morphology in HCEnCs solely from female donors in the [O2]Acondition. ATP levels were significantly higher at [O2]2.5than at [O2]Ain HCEnCs from female donors only, but were not affected by E2. Our findings demonstrate the resilience of HCEnCs against hyperoxic stress. The effects of hyperoxia and E2 on HCEnCs from female donors suggest cell sex-specific mechanisms of toxicity and hormonal influences.