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Yue Li, Tongrong Zhou, Paul A Edwards, Hua Gao, Xiaoxi Qiao; Metformin inhibits oxidative stress and enhances anti-oxidative signaling pathway in human retinal vascular endothelial cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5479. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Oxidative stress is increased in diabetic retinopathy (DR). Metformin exhibited a significant anti-inflammatory effect in diabetic retinal tissue and was associated with decreased severity of DR in type 2 diabetes patients. In this study, we investigated whether metformin could regulate oxidative stress in human retinal vascular endothelial cells (hRVECs).
Human RVECs (ACBRI 181) were stimulated with high glucose (30 mM) or TNFα (2.5 ng/mL), and treated with various doses of metformin. Intracellular reactive oxygen species (ROS) were measured using the cell permeant reagent 2',7'-Dichlorodihydrofluorescein diacetate (DCF). Expression of nuclear factor erythroid 2-related factor (Nrf2) and its downstream antioxidant enzyme heme oxygenase-1 (HO-1) were examined by immunoblot.
ROS production was markedly enhanced by both high glucose and TNFα in hRVECs. High glucose-trigged increase of ROS was significantly reduced by 10 and 20 mM metformin. Pretreatment of metformin at 5 to 20 mM also dose-dependently abolished TNFα-induced increase of ROS production in hRVECs. Correspondingly, metformin treatment was capable of boosting the expressions of Nrf-2 and HO-1, key molecules of antioxidant response element signaling pathway in hRVECs.
Metformin attenuates oxidative stress induced by both high glucose and inflammation in hRVECs, probably by activating the Nrf2/HO-1 antioxidant signaling pathway. Such anti-oxidative effect of metformin further supplements our previous findings on the anti-angiogenic and anti-inflammatory effects of metformin, indicating multiple benefits of metformin in different aspects of DR involved in diabetes microvascular complications.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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