Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy.

We have investigated the contributing role of monosodium urate (MSU) to the pathological processes associated with the induction of diabetic retinopathy (DR). In human postmortem retinas and vitreous from donors with DR, we have found a significant increase in MSU levels which correlated with the presence of inflammatory markers and enhanced expression of xanthine oxidase. Same elevation in MSU levels was also detected in serum and vitreous of streptozotocin-induced diabetic rats (STZ-rats) analyzed at 8 weeks of hyperglycemia. Furthermore, treatments of STZ-rats with the hypouricemic drugs allopurinol (50 mg/kg) and benzbromarone (10 mg/kg) given every other day resulted in a significant decrease of retinal and plasma levels of inflammatory cytokines and adhesion factors, a marked reduction of hyperglycemia-induced retinal leukostasis, and restoration of retinal blood barrier function. These results were associated with effects of the hypouricemic drugs on down-regulating diabetes-induced levels of oxidative stress markers as well as expression of components of the NLRP3 inflammasome such as NLRP3, TLR4 and IL-1β. The outcomes of these studies support a contributing role of MSU in diabetes-induced retinal inflammation and suggest that asymptomatic hyperuricemia should be considered as a risk factor for DR induction and progression.