Resveratrol exhibits an effect on attenuating retina inflammatory condition and damage of diabetic retinopathy via PON1

Abstract Diabetic retinopathy (DR), an obstacle of the visual microvascular system, is a serious complication of diabetic patients. Paraoxonase 1 (PON1) has been extensively evaluated as a genetic candidate for diabetic microvascular complications, and PON1 is associated with DR. In this study, the biological functions of PON1 and its related proteins were determined via gene ontology (GO) enrichment analysis; we demonstrated that treatment with resveratrol alleviated retinal inflammatory activities to evaluate its protective effects on streptozotocin (STZ)-induced diabetic rats and high-glucose (HG) stimulated rat retinal endothelial cells (RRECs). The GO enrichment analysis suggested that PON1 may regulate inflammatory responses and microvascular complications in DR. In an in vivo study, resveratrol significantly recovered the insulin level and PON1 expression and activity, as well as clearly reduced the retinal vascular permeability, retinal AGEs, LDL, Ox-LDL, caspase3 activity, retinal damage, IL-1β, IL-6, TNFα, VEGF, IFNγ and MCP-1 in STZ-diabetic rats. Moreover, resveratrol reduced the caspase3 activity and Ox-LDL expression in HG stimulated RRECs. However, its protective effect was a deficiency in PON1-silenced RRECs. PON1 is a pivotal modulator in the role of resveratrol in reversing the RREC damage induced by HG. Furthermore, we found that resveratrol exhibits an effect on attenuating the retinal inflammatory condition and damage of DR via PON1. Our study suggests that resveratrol-induced PON1 in the retina may be a promising therapeutic strategy to prevent diabetes-related retinopathy.