Chronic
hyperglycemia is an important risk factor involved in the onset and progression of
diabetic retinopathy (DR). Among other effectors,
aldose reductase (AR) has been linked to the pathogenesis of this degenerative disease. The purpose of this study was to investigate whether the novel AR inhibitor,
beta-glucogallin (BGG), can offer protection against various
hyperglycemia-induced abnormalities in human adult
retinal pigment epithelial (ARPE-19) cells. AR is an
enzyme that contributes to cellular stress by production of
reactive oxygen species (ROS) under high
glucose conditions. A marked decrease in cell viability (from 100% to 78%) following long-term exposure (4 days) of RPE cells to high
glucose (HG) was largely prevented by
siRNA-mediated knockdown of AR gene expression (from 79% to 97%) or inhibition using
sorbinil (from 66% to 86%). In HG, BGG decreased
sorbitol accumulation (44%), ROS production (27%) as well as ER stress (22%). Additionally, we demonstrated that BGG prevented loss of mitochondrial membrane potential (
MMP) under HG exposure. We also showed that AR inhibitor pretreatment reduced
retinal microglia-induced apoptosis in APRE-19 cells. These results suggest that BGG may be useful as a therapeutic agent against
retinal degeneration in the diabetic eye by preventing RPE cell death.