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. (July 2020)

• Record Type: Journal Article
• Authors: Du, Jingxia; Wang, Ying; Tu, Yuanyuan; Guo, Yang; Sun, Xiaodong; Xu, Xun; Liu, Xiaojuan; Wang, Li; Qin, Xiao; Zhu, Manhui; Song, E.
• Is Part Of: Experimental eye research. Volume 196(2020)
• Publication Date: 2020-07
• Subjects: Diabetic retinopathy (DR) -- Prodrug of epigallocatechin-3-gallate (pro-EGCG) -- Retinal Müller cells -- Reactive oxygen species (ROS) -- Thioredoxin interacting protein (TXNIP) -- NACHT -- LRR and PYD domain-containing protein 3 (NLRP3) inflammasome -- Proangiogenic factor; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2020.108065
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Diabetic retinopathy (DR) is a neurovascular complication of diabetes mellitus that leads to blindness in the working-age population. Retinal Müller 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 Müller cells. A prodrug of EGCG (pro-EGCG) enhances the bioavailability of EGCG. In an in vitro model of high glucose-stimulated Müller 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, Müller cell proliferation, and production of the pro-angiogenic factors VEGF and HGF. In summary, pro-EGCG mitigated hyperglycaemia-challenged Müller cell proliferation and pro-angiogenic factor production by inhibiting ROS/TXNIP/NLRP3 inflammasome signalling, implying a potential therapeutic strategy for DR. Highlights: Müller 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 domains-containing protein 3 (NLRP3) inflammasome axis to promote proliferative DR. In an in vitro model of high glucose-stimulated Müller cells, pro-EGCG inhibited proliferation and pro-angiogenic factor production by downregulating ROS/TXNIP/NLRP3 inflammasome axis activity. In a mouse DR model, pro-EGCG reduced ROS accumulation, NLRP3 inflammasome activation, Müller cell proliferation, and production of the pro-angiogenic factors VEGF and HGF. Pro-EGCG mitigated hyperglycaemia-challenged Müller cell proliferation and pro-angiogenic factor production by inhibiting ROS/TXNIP/NLRP3 inflammasome signalling.