Although blackcurrant has several health benefits, such as antioxidant and anti-inflammatory properties, its effects on the retina remain unclear. In this study, we investigated the efficacy of black currant extract (BCE) in an in vitro and in vivo model of dry age-related macular degeneration (AMD) induced by blue light. Dry macular degeneration is characterized by the abnormal accumulation of lipofuscin (e.g., N-retinylidene-N-retinylethanolamine, A2E) in the retina. Blue light (BL) significantly decreased the viability of A2E-laden human retinal pigment epithelial cells (ARPE-19). However, BCE treatment protected ARPE-19 cells from A2E and BL. A2E, which is oxidized by blue light, generates reactive oxygen species in RPE cells. Treatment with BCE significantly decreased (80.8%) reactive oxygen species levels induced by A2E and BL in a concentration-dependent manner. BCE inhibited A2E accumulation in ARPE-19 cells and significantly downregulated the expression of genes increased by A2E and BL in ARPE-19 cells. In vivo, oral administration of BCE (25–100 mg/kg) ameliorated ocular lesions of BL-induced retinal damage in a mouse model and rescued the thickness of the whole retina, photoreceptor segment layer, outer nuclear layer, and inner nuclear layer. The decrease in the number of nuclei in the outer nuclear layer induced by BL was also rescued by BCE. Additionally, BCE administration rescued (40.0%) the BL-induced reduction in the expression level of superoxide dismutase 1. Taken together, our results suggest that BCE may have preventive and therapeutic effects on dry AMD through its antioxidant activity and inhibition of lipofuscin accumulation in the retina.

Background: N-retinylidene-N-retinylethanolamine (A2E) is a component of drusen that accumulates in retinal cells and induces oxidative stress through photooxidation, such as blue light (BL). We found that the heme oxygenase 1 (HMOX1) gene responds sensitively to photooxidation by the BL of A2E in retinal pigment epithelial (RPE) cells, and we sought to identify the transcription factors and coactivators involved in the upregulation of HMOX1 by A2E and BL. Methods: A2E-laden human RPE cells (ARPE-19) were exposed to BL (430 nm). RNA sequencing was performed to identify genes responsive to BL exposure. Chromatin immunoprecipitation and RT-qPCR were performed to determine the regulation of HMOX1 transcription. Clinical transcriptome data were used to evaluate HMOX1 expression in patients with age-related macular degeneration (AMD). Results: In ARPE-19 cells, the expression of HMOX1, one of the NF-κB target genes, was significantly increased by A2E and BL. The binding of RELA and RNA polymerase II to the promoter region of HMOX1 was significantly increased by A2E and BL. Lysine methyltransferase 2A (MLL1) plays an important role in H3K4me3 methylation, NF-κB recruitment, chromatin remodeling at the HMOX1 promoter, and, subsequently, HMOX1 expression. The retinal tissues of patients with late-stage AMD showed significantly increased expression of HMOX1 compared to normal retinal tissues. In addition, the expression levels of MLL1 and HMOX1 in retinal tissues were correlated. Conclusions: Taken together, our results suggest that BL induces HMOX1 expression by activating NF-κB and MLL1 in RPE cells.