6533b85efe1ef96bd12bfea9

RESEARCH PRODUCT

Docosahexaenoic acid protects human RPE cells against oxidative stress via PI3K/Akt m-TOR/p70-p85S6K pathways

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Purpose Oxidative Stress (OS) plays a critical role in the pathogenesis of age-related macular degeneration (AMD), especially by targeting the retinal pigment epithelium (RPE). Dietary habits with high consumption of docosahexaenoic acid (DHA) have been shown to prevent the development and evolution of AMD. Nevertheless, it is still unclear how DHA affects AMD. Our study aimed to investigate the involvement of the PI3K/Akt and m-TOR/p70-p85S6K pathways in human RPE cells after induction of OS, and then to assess the effect of DHA in the signaling pathways and in the protection against RPE cell death. Methods For this purpose, we used ARPE-19 cells exposed to the prooxidant agent, tert-butyl hydroperoxide (t-BHP). Results We found that exposing cells to t-BHP (400µM) showed complete inhibition of Akt and p70/p85S6K active forms. However in cells enriched with DHA (20µM) and then exposed to t-BHP (400µM), we demonstrated that Akt and p85S6K, but not p70S6K, remained phosphorylated for a longer time after stress. In addition there was a 2.6-fold decrease in the number of necrotic cells after 48hours of t-BHP treatment, as assessed by flow cytometry. Conclusion Our study suggests that 1/ PI3K/Akt and m-TOR/P70-p85S6K pathways play an important role in OS, 2/DHA protects RPE cells from apoptosis and necrosis triggered by OS by enhancing the phosphorylation of Akt and p85S6K.