Resvega induces autophagy and prevents ARPE‐19 cell damage during proteasome inhibition

Purpose Impaired autophagic and proteasomal cleansing has been documented in retinal pigment epithelial (RPE) cells and age‐related macular degeneration (AMD) pathology. Omega fatty acids and resveratrol has been shown to be cytoprotective in RPE cells. We examined effects of commercial Resvega on the regulation of autophagy and cytoprotection in ARPE‐19 cells under proteasome inhibition. Methods Protein aggregation was induced with 1 mM MG‐132 and autophagy was inhibited with bafilomycin A1. Resvega that includes vitamin C 240 mg, E 30 mg, zinc 12.5 mg, copper 1 mg, omega‐3 665 mg, lutein 10 mg, zeaxanthin 2 mg and resveratrol 30 mg was used solely and together with proteasome inhibition up to 48 h. p62 (SQSTM1), LC3 (microtubule‐associated protein 1A/1B‐light chain 3) and Hsp70 (Heat shock protein 70) were analyzed by Western blotting (WB). Tandem fluorescently tagged LC3 (GFP‐mCherry‐LC3) transfection was used to study autophagy flux in fluorescence microscopy. Results Inhibition of proteasomes with MG‐132 upregulated Hsp70, autophagy markers p62 and LC3 detected in WB. Simultaneous treatment with MG‐132 and Resvega corresponding 25 μM resveratrol concentration highly increased amount of LC3‐II, but decreased p62 and Hsp70. Moreover, Resvega provided a clear cytoprotection under proteasome inhibition. Fluorescence microscopy showed increased autophagy flux with GFP‐mCherry‐LC3 Resvega treatment and autophagy inhibition resulted accumulation of p62 and LC3‐II. Conclusions This data showed how Resvega was able to induce autophagy and clear protein waste caused by proteasome inhibition in ARPE‐19 cell line. Resvega has a potential in the prevention and treatment of RPE damage and AMD.