Probucol attenuates high glucose-induced Muller cell damage through enhancing the Nrf2/p62 signaling pathway

PurposeThis study investigated the protective effect of probucol on Muller cells exposed to high glucose conditions and examined potential mechanisms of action.MethodsPrimary human retinal Muller cells were incubated with high glucose (HG, 35 mM) in the present or absence of different concentrations of probucol for 24 h. Cell viability was determined using the CCK-8 method. Mitochondrial membrane potential (MMP) was measured using JC-1 staining and cell cycle by flow cytometry. The expression of nuclear factor E2-related factor 2 (Nrf2), glutamate-cysteine ligase catalytic subunit, and p62 was quantified using quantitative polymerase chain reaction and western blot.ResultsWe found that HG inhibited cell proliferation, arrested cell cycle, and increased MMP in human Muller cells. Probucol activated the Nrf2/p62 pathway and upregulated the anti-apoptotic protein, Bcl2, and attenuated HG-mediated damage in Muller cells.ConclusionsOur results suggest that probucol may protect Muller cells from HG-induced damage through enhancing the Nrf2/p62 signaling pathway.