In this study, we investigated the anti-age-related macular degeneration (AMD) effects of SF, a 1:1 mixture of 7,17-dihydroxy-docosahexaenoic acid (DHA) and 10,7-dihydroxy-DHA, in human retinal pigmented epithelial (RPE) cells. Cytotoxicity in RPE cells was first confirmed, while non-toxicity was confirmed at concentrations below 2 μg/mL. Irradiation of RPE cells with bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E) and blue light resulted in a cell viability of less than 80 %, whereas SF treatment increased cell viability in a concentration-dependent manner. In addition, apoptosis induced by A2E and blue light was found to be regulated by lutein and SF. Lutein and SF treatments regulated the Bcl family, with SF showing stronger efficacy in regulating Bax and Bad expression than lutein. Furthermore, SF affected MAPKs, particularly by regulating the expression of JNK and p-38. SF may have similar effects on the expression of inflammatory proteins and pro-inflammatory cytokines at 5 μg/mL and 2 μg/mL concentrations of lutein and SF. Lastly, SF appeared to regulate the expression of Nrf2, OH-1, SOD1, and 4-HNE, which are biomarkers of oxidative and carbonyl stress. In conclusion, SF may exert its protective effects by regulating various signaling pathways in response to A2E and blue light stimulation at the cellular level.