Jia-Hao Feng1, Xiao-Wei Dong1, Hao-Li Yu2, Wei Shen1, Xian-Yu Lv1, Rong Wang1, Xue-Xiang Cheng3, Fei Xiong2, Xiao-Long Hu4, Hao Wang5. 1. State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. 2. State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, Southeast University, Nanjing 210009, People's Republic of China. 3. Hubei Fenghuang Baiyunshan Pharmaceutical Co., Ltd, Macheng 438300, People's Republic of China. 4. State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. Electronic address: huxiaolong@cpu.edu.cn. 5. State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. Electronic address: wanghao@cpu.edu.cn.
Abstract
BACKGROUND: Blue light can directly penetrate the lens and reach the retina to induce retinal damage, causing dry age-related macular degeneration (dAMD). Cynaroside (Cyn), a flavonoid glycoside, was proved to alleviate the oxidative damage of retinal cells in vitro. However, whether or not Cyn also exerts protective effect on blue light-induced retinal degeneration and its mechanisms of action are unclear. PURPOSE: This study aims to evaluate the protective effects of Cyn against blue-light induced retinal degeneration and its underlying mechanisms in vitro and in vivo. STUDY DESIGN/ METHODS: Blue light-induced N-retinylidene-N-retinylethanolamine (A2E)-laden adult retinal pigment epithelial-19 (ARPE-19) cell damage and retinal damage in SD rats were respectively used to evaluate the protective effects of Cyn on retinal degeneration in vitro and in vivo. MTT assay and AnnexinV-PI double staining assay were used to evaluate the in vitro efficacy. Histological analysis, TUNEL assay, and fundus imaging were conducted to evaluate the in vivo efficacy. ELISA assay, western blot, and immunostaining were performed to investigate the mechanisms of action of Cyn. RESULTS: Cyn decreased the blue light-induced A2E-laden ARPE-19 cell damage and oxidative stress. Intravitreal injection of Cyn (2, 4 μg/eye) reversed the retinal degeneration induced by blue light in SD rats. Furthermore, Cyn inhibited the nuclear translocation of NF-κB and induced autophagy, which led to the clearance of overactivated pyrin domain containing 3 (NLRP3) inflammasome in vitro and in vivo. CONCLUSION: Cyn protects against blue light-induced retinal degeneration by modulating autophagy and decreasing the NLRP3 inflammasome.
BACKGROUND: Blue light can directly penetrate the lens and reach the retina to induce retinal damage, causing dry age-related macular degeneration (dAMD). Cynaroside (Cyn), a flavonoid glycoside, was proved to alleviate the oxidative damage of retinal cells in vitro. However, whether or not Cyn also exerts protective effect on blue light-induced retinal degeneration and its mechanisms of action are unclear. PURPOSE: This study aims to evaluate the protective effects of Cyn against blue-light induced retinal degeneration and its underlying mechanisms in vitro and in vivo. STUDY DESIGN/ METHODS: Blue light-induced N-retinylidene-N-retinylethanolamine (A2E)-laden adult retinal pigment epithelial-19 (ARPE-19) cell damage and retinal damage in SD rats were respectively used to evaluate the protective effects of Cyn on retinal degeneration in vitro and in vivo. MTT assay and AnnexinV-PI double staining assay were used to evaluate the in vitro efficacy. Histological analysis, TUNEL assay, and fundus imaging were conducted to evaluate the in vivo efficacy. ELISA assay, western blot, and immunostaining were performed to investigate the mechanisms of action of Cyn. RESULTS:Cyn decreased the blue light-induced A2E-laden ARPE-19 cell damage and oxidative stress. Intravitreal injection of Cyn (2, 4 μg/eye) reversed the retinal degeneration induced by blue light in SD rats. Furthermore, Cyn inhibited the nuclear translocation of NF-κB and induced autophagy, which led to the clearance of overactivated pyrin domain containing 3 (NLRP3) inflammasome in vitro and in vivo. CONCLUSION:Cyn protects against blue light-induced retinal degeneration by modulating autophagy and decreasing the NLRP3 inflammasome.