Procyanidin protects human retinal pigment epithelial cells from high glucose by inhibiting autophagy

Abstract

Purpose The damage of hyperglycemia to the retinal pigment epithelial (RPE) cells is a critical event in diabetic retinopathy (DR). Procyanidin (PC), a kind of polyphenol compounds, has shown to be effective in preventing and treating diabetes as well as its complications, in which autophagy disorder is involved in the pathological mechanism. However, it remains unclear whether PC can play a protective role in DR by regulating the autophagy of RPE. Here, the effect of PC on RPE under high glucose conditions and the role of autophagy were investigated. Materials and Methods The cell viability of ARPE‐19, a human RPE cell line, was detected by cell counting kit‐8 (CCK‐8) and the apoptosis rate was measured by flow cytometry. The protein expressions of apoptosis markers, including Bax, Bcl‐2, and Caspase‐3, as well as autophagy markers including LC3, p62, p53, and mTOR were detected by Western blotting. Autophagic flux in ARPE‐19 cells was detected by transfection with Ad‐mCherry‐GFP‐LC3B. Results Under high glucose conditions, the viability of ARPE‐19 was decreased and the apoptosis rate increased, the protein expressions of Bax, Caspase‐3, LC3‐II/LC3‐I, and p‐p53 were all increased and the expressions of Bcl‐2, p62, and p‐mTOR decreased, and autophagic flux was increased compared with that of the controls. Treatment with PC weakened all these changes caused by high glucose. When rapamycin (RPM), an autophagy agonist was added, the cell viability of ARPE‐19 by PC treatment was decreased while the apoptosis was increased. Conclusions Our findings indicate that through the p53/mTOR autophagy pathway, PC may protect RPE cells from high glucose‐induced injury.

Ascorbic acid protects retinal pigment epithelial cells from high glucose by inhibiting the NF‐κB signal pathway through MALAT1/IGF2BP3 axis

“…DR is one of the typical diabetes chronic complication, the rise of blood sugar cause serious damage to RPE cells. 23 Recovery of the hyperglycaemia-induced abnormal processes including oxidative stress and inflammation may be helpful to repress the RPE cell damage of DR. 24 According to existing research, it is well recognized that IGF2BP3 can activate the NF-κB signalling pathway and promote pro-inflammatory response. 25 Therefore, in our study, we supplemented the relevant mechanism that the inhibition of IGF2BP3 alleviated the inflammation and apoptosis of the HG-induced RPE cell injury in vitro model.…”

“…DR is one of the typical diabetes chronic complication, the rise of blood sugar cause serious damage to RPE cells 23 . Recovery of the hyperglycaemia‐induced abnormal processes including oxidative stress and inflammation may be helpful to repress the RPE cell damage of DR 24 .…”

The role of the mTOR pathway in diabetic retinopathy

“…Consistently, Zhang et al showed that high glucose conditions mediate the damage to ARPE-19 and increase its autophagy as well as apoptotic markers (p-p53, Bcl-2, and p62), and that these damages can be reversed by the autophagy inhibitor 3-methyladenine (3-MA), indicating a dysregulation of the autophagic process (149). This last observation was further confirmed by the same group, pointing out the beneficial effect of procyanidin, a member of the flavonoids, which inhibits autophagy (150). Interestingly, these beneficial effects were reversed when the autophagy agonist rapamycin was added to procyanidin treatment.…”

Network pharmacology mechanism of Scutellarin to inhibit RGC pyroptosis in diabetic retinopathy

“…CASP3 has been involved in apoptosis, which cause DR through retinal damage 48 . What's more, under high glucose conditions, the viability of retinal pigment epithelial cells was decreased and the apoptosis rate increased, the expression of CASP3, Bax were increased and the expression of Bcl-2 decreased 49 . Meanwhile, a study found that 50 STZ injection caused the increased expression levels of DNMT1 and DNMT3B, which induced DNA hypermethylation, inhibited the expression of CDKN2B and facilitated the damages of RGC.…”