Vitamin D(3) Protects against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of the ROS/TXNIP/NLRP3 Inflammasome Pathway

PURPOSE: This study aimed to evaluate the mechanisms underlying the effects of 1,25-dihydroxyvitamin D (vitamin D(3)) on diabetes-induced retinal vascular damage and retinal vascular endothelial cell apoptosis. METHODS: Diabetic and control rats were randomly assigned to receive vitamin D(3) or vehicle for 6 months. Additionally, human retinal microvascular endothelial cells (HRMECs) were incubated in normal or high-glucose medium with or without vitamin D(3). Morphological changes in retinal tissues and retinal vascular permeability were examined, and cellular apoptosis was detected by fluorescence staining. Intracellular reactive oxygen species (ROS) levels were determined using fluorescent probes. Proteins were examined by Western blotting. RESULTS: Vitamin D(3) significantly downregulated intracellular ROS and inhibited TRX-interacting protein (TXNIP)/NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathway activation. Additionally, vitamin D(3) reduced vascular endothelial growth factor (VEGF) expression and the Bax/Bcl-2 ratio. These changes were associated with retinal recovery and with decreases in retinal vascular permeability and retinal capillary cell apoptosis. CONCLUSIONS: Vitamin D(3) decreases diabetes-induced ROS and exerts protective effects against retinal vascular damage and cell apoptosis in association with inhibition of the ROS/TXNIP/NLRP3 inflammasome pathway. Understanding the mechanisms of action of vitamin D(3) has important implications for preventing and treating inflammatory-related illnesses such as diabetic retinopathy.