Abstract
Summary
We hypothesized that a novel mechanism exists where HMGB1and NADPH oxidase (NOX)‐derived ROS are mutually enhanced in the diabetic retina, which may be a novel mechanism for promoting upregulation of retinal apoptotic markers induced by diabetes. To test this hypothesis we analyzed the vitreous samples from PDR and nondiabetic patients, retinas from rats and human retinal microvascular endothelial cells. We found that HMGB1 and the oxidative stress marker protein carbonyl content levels in the vitreous fluid from PDR patients were significantly higher than in controls. There was a significant positive correlation between vitreous fluid levels of HMGB1 and the levels of protein carbonyl content. HMGB1 enhanced interleukin‐1β, ROS, NOX2, and PARP‐1 and cleaved caspase‐3 expression by HRMEC. Diabetes and intravitreal injection of HMGB1 in normal rats induced significant upregulation of ROS, NOX2, PARP‐1 and cleaved caspase‐3 in the retina. Constant glycyrrhizin and apocynin intake from onset of diabetes did not affect the metabolic status of the diabetic rats, but restored these increased mediators to control values. Our results suggest that there is a mutual enhancement between HMGB1 and NOX‐derived ROS in the diabetic retina.