Cyanidin-3-O-glucoside from blueberry anthocyanin extracts protects ARPE-19 cells against high glucose damage via REDD1/GSK38 pathway

The retinal pigment epithelium (RPE) serves dual roles: it acts as a selective barrier and also as a regulator for the photoreceptor layer situated above it. The RPE is considered a crucial target for halting the development and progression of diabetic retinopathy (DR). This study focuses on understanding the protective role of blueberry anthocyanin extracts (BAEs), particularly its anti-oxidant constituent, cyanidin-3-O-glucoside (C3G), against damage to RPE cells induced by high glucose (HG) levels. The findings revealed that the BAEs mitigated damage to HG-induced ARPE-19 cells by decreasing the intracellular reactive oxygen species (ROS) levels, which improved cell morphology and cell viability (p < 0.01). Importantly, these cytoprotective effects were linked to the C3G rich in BAEs. The underlying mechanism may involve C3G interrupting the ROS generation feedback loop by downregulating REDD1 expression, which in turn enhanced the retinal Nrf2 antioxidant response to HG through the promotion of the GSK38 phosphorylation at Ser-9. Moreover, C3G suppressed VEGFA expression by inhibiting REDD1 levels in HG-induced ARPE-19 cells, subsequently preventing an increase in vascular permeability. In conclusion, this study suggested that the C3G relieved HG-induced oxidative stress damage in ARPE19 cells via REDD1/GSK38 pathway and inhibited an increase in vascular permeability by downregulating VEGFA expression. These insights could shed light on how this natural bioactive compound can help manage HGassociated eye disorders like DR.