A prodrug of epigallocatechin-3-gallate alleviates high glucose-induced pro-angiogenic factor production by inhibiting the ROS/TXNIP/NLRP3 inflammasome axis in retinal Müller cells.

Abstract Diabetic retinopathy (DR) is a neurovascular complication of diabetes mellitus that leads to blindness in the working-age population. Retinal Muller cells proliferate and produce pro-angiogenic factors, including vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), via the reactive oxygen species (ROS)/thioredoxin interacting protein (TXNIP)/NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome axis to promote proliferative DR. Epigallocatechin-3-gallate (EGCG) plays anti-oxidant, anti-inflammatory, anti-proliferative and anti-angiogenic roles in Muller cells. A prodrug of EGCG (pro-EGCG) enhances the bioavailability of EGCG. In an in vitro model of high glucose-stimulated Muller cells, pro-EGCG inhibited proliferation and pro-angiogenic factor production by down-regulating the activity of the ROS/TXNIP/NLRP3 inflammasome axis. In a mouse DR model, pro-EGCG reduced ROS accumulation, NLRP3 inflammasome activation, Muller cell proliferation, and production of the pro-angiogenic factors VEGF and HGF. In summary, pro-EGCG mitigated hyperglycaemia-challenged Muller cell proliferation and pro-angiogenic factor production by inhibiting ROS/TXNIP/NLRP3 inflammasome signalling, implying a potential therapeutic strategy for DR.