Cyanidin 3-O glucoside Ameliorate Nickel Chloride-induced VEGF and Interleukin-8 in Retinal Pigment Epithelial Cells

The mechanisms of age-related macular degeneration (AMD) are complex and challenging to treat. Clinically, it is classified into two types: dry and wet. Typically, oxidative stress, inflammation, or angiogenesis are key pathogenic factors. Nickel chloride, a compound commonly found in environmental pollutants or alloy components, often causes oxidative stress in cells, human allergies, or cancer metastasis. Therefore, the primary aim of this experiment is to explore whether nickel chloride causes oxidative stress and inflammation in retinal pigment epithelial cells, and subsequently, whether antioxidants or health supplements can mitigate these adverse cellular responses. Our results, utilizing MTT analysis, indicate that nickel chloride causes toxicity in retinal pigment epithelial cells, leading to increased reactive oxygen species (ROS) within cells and changes in cell morphology, making them elongated and dispersed. Through PI staining and flow cytometry, we found that nickel chloride induces cell cycle arrest at the G2/M phase. Quantitative PCR revealed increased mRNA expression of IL-8 and VEGF. Western blotting demonstrated an increase in HIF-1α, HO-1, HK2, and SOD2, while catalase levels decreased, and the expression of autophagy-related proteins increased. ELISA results showed that nickel chloride promotes the secretion of IL-8 and VEGF in retinal pigment epithelial cells. Further studies with lutein, anthocyanin (cyanidin 3-O-glucoside, C3G), N-acetylcysteine, and Metformin revealed that anthocyanin (C3G) could inhibit VEGF protein expression and IL-8-induced inflammation. Nickel chloride treatment of retinal pigment epithelial cells may serve as a valuable cell model for studying AMD.