Vitamin D3 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 D3) on diabetes-induced retinal vascular damage and retinal vascular endothelial cell apoptosis. Methods. Diabetic and control rats were randomly assigned to receive vitamin D3 or vehicle...

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Main Authors: Li Lu, Qianyi Lu, Wei Chen, Jingwen Li, Chunxia Li, Zhi Zheng
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2018/8193523
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author Li Lu
Qianyi Lu
Wei Chen
Jingwen Li
Chunxia Li
Zhi Zheng
author_facet Li Lu
Qianyi Lu
Wei Chen
Jingwen Li
Chunxia Li
Zhi Zheng
author_sort Li Lu
collection DOAJ
description Purpose. This study aimed to evaluate the mechanisms underlying the effects of 1,25-dihydroxyvitamin D (vitamin D3) on diabetes-induced retinal vascular damage and retinal vascular endothelial cell apoptosis. Methods. Diabetic and control rats were randomly assigned to receive vitamin D3 or vehicle for 6 months. Additionally, human retinal microvascular endothelial cells (HRMECs) were incubated in normal or high-glucose medium with or without vitamin D3. 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 D3 significantly downregulated intracellular ROS and inhibited TRX-interacting protein (TXNIP)/NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathway activation. Additionally, vitamin D3 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 D3 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 D3 has important implications for preventing and treating inflammatory-related illnesses such as diabetic retinopathy.
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spelling doaj-art-b009465e9fe94b95a6ecba175ff6745c2025-08-20T03:39:17ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/81935238193523Vitamin D3 Protects against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of the ROS/TXNIP/NLRP3 Inflammasome PathwayLi Lu0Qianyi Lu1Wei Chen2Jingwen Li3Chunxia Li4Zhi Zheng5Department of Ophthalmology, Anhui Provincial Hospital The First Affiliated Hospital of University of Science and Technology of China, Hefei 230001, ChinaDepartment of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou 215006, ChinaDepartment of Ophthalmology, Shanghai First People’s Hospital, Shanghai Jiao Tong University, Shanghai 200080, ChinaDepartment of Ophthalmology, Shanghai TCM-Integrated Hospital, Shanghai University of TCM, 230 Baoding Road, Shanghai 200082, ChinaDepartment of Ophthalmology, Shanghai TCM-Integrated Hospital, Shanghai University of TCM, 230 Baoding Road, Shanghai 200082, ChinaDepartment of Ophthalmology, Shanghai First People’s Hospital, Shanghai Jiao Tong University, Shanghai 200080, ChinaPurpose. This study aimed to evaluate the mechanisms underlying the effects of 1,25-dihydroxyvitamin D (vitamin D3) on diabetes-induced retinal vascular damage and retinal vascular endothelial cell apoptosis. Methods. Diabetic and control rats were randomly assigned to receive vitamin D3 or vehicle for 6 months. Additionally, human retinal microvascular endothelial cells (HRMECs) were incubated in normal or high-glucose medium with or without vitamin D3. 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 D3 significantly downregulated intracellular ROS and inhibited TRX-interacting protein (TXNIP)/NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathway activation. Additionally, vitamin D3 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 D3 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 D3 has important implications for preventing and treating inflammatory-related illnesses such as diabetic retinopathy.http://dx.doi.org/10.1155/2018/8193523
spellingShingle Li Lu
Qianyi Lu
Wei Chen
Jingwen Li
Chunxia Li
Zhi Zheng
Vitamin D3 Protects against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of the ROS/TXNIP/NLRP3 Inflammasome Pathway
Journal of Diabetes Research
title Vitamin D3 Protects against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of the ROS/TXNIP/NLRP3 Inflammasome Pathway
title_full Vitamin D3 Protects against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of the ROS/TXNIP/NLRP3 Inflammasome Pathway
title_fullStr Vitamin D3 Protects against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of the ROS/TXNIP/NLRP3 Inflammasome Pathway
title_full_unstemmed Vitamin D3 Protects against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of the ROS/TXNIP/NLRP3 Inflammasome Pathway
title_short Vitamin D3 Protects against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of the ROS/TXNIP/NLRP3 Inflammasome Pathway
title_sort vitamin d3 protects against diabetic retinopathy by inhibiting high glucose induced activation of the ros txnip nlrp3 inflammasome pathway
url http://dx.doi.org/10.1155/2018/8193523
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