Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis.

Background: Diabetic retinopathy (DR), as a frequent complication of diabetes mellitus, is a common cause of vision impairment and blindness. Microglial activation plays an important role in the pathological cascade of DR, and novel potential therapeutics is needed to interfere with this process. Petunidin (PET) is one of the most abundant natural anthocyanins with the biological activities of anti-inflammation, anti-cancer, and anti-microbial.

Objective: The purpose of this study is to investigate the effect of PET against lipopolysaccharide (LPS)-induced retinal microglia inflammatory response as well as the underpinning mechanism.

Methods: Cell viability was determined using MTT assay. Cytokines secretion was determined using ELISA assay. iTRAQ-based proteomic analysis was used for the identification of differentially expressed proteins. Western blot analysis, Co-IP and immunofluorescence analysis were applied in the study.

Results: The results showed that PET pre-treatment significantly reduced LPS-induced cytokines secretion in BV2 cells and primary retinal microglia, as well as lipocalin 2 (LCN2) upregulation in BV2 cells by suppressing activation of O-GlcNAc modification and activation of NF‑κB. Further study revealed that PET inactivated NF‑κB by down-regulating OGT in BV2 cells, indicating that the protective effect of PET against LPS-induced retinal microglia inflammatory response was achieved by regulating OGT/NF-κB/LCN2 axis.

Conclusion: Our findings may contribute to the potential clinical use of PET in treating DR and suggest OGT/NF-κB/LCN2 axis may be the potential therapeutic target of this disease.