Protective mechanisms of polyphenol-enriched fraction of Vaccinium uliginosum L. Against blue light-induced cell death of human retinal pigmented epithelial cells

•Gene expression in inflammation and apoptosis are regulated by blue light and A2E.•Polyphenol fraction of V.U (FH) protects ARPE-19 from blue light and A2E.•FH inhibits the accumulation of A2E and increases the removal of A2E from RPE cells. Accumulation of N-retinylidene-N-retinylethanolamine (A2E) in retinal pigment epithelial cells is implicated in the pathogenesis of age-related macular degeneration (AMD). A recent study has demonstrated that the polyphenol-enriched fraction of Vaccinium uliginosum L. (FH) reduces retinal damage induced by blue light in a mouse model. However, the underlying mechanism of its protective effect remains unclear. Here, we revealed that blue light irradiation of A2E-laden ARPE-19 cells can alter the transcription of genes belonging to TNFα signaling, UV response, complement, p53, and apoptosis pathways. FH treatment of ARPE-19 cells inhibited blue light-induced transcriptional activity of NF-kB and AP1 and activation of C3 complement. Additionally, FH protected ARPE-19 cells from blue light-induced apoptosis. Finally, we showed that FH inhibits the intracellular accumulation of A2E and induces the removal of A2E from retinal pigment cells. Taken together, our study revealed the protective mechanisms of FH against blue light-induced damage of A2E-laden RPE cells.