Trimethylamine-N-Oxide Promotes High-Glucose-Induced Dysfunction and NLRP3 Inflammasome Activation in Retinal Microvascular Endothelial Cells
Introduction. Along with blood glucose levels, diabetic retinopathy (DR) development also involves endogenous risk factors, such as trimethylamine-N-oxide (TMAO), a product of intestinal flora metabolic disorder, which exacerbates diabetic microvascular complications. However, the effect of TMAO on...
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| Format: | Article |
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Wiley
2023-01-01
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| Series: | Journal of Ophthalmology |
| Online Access: | http://dx.doi.org/10.1155/2023/8224752 |
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| author | Lidan Xue Lili Huang Yajing Tian Xin Cao Yu Song |
| author_facet | Lidan Xue Lili Huang Yajing Tian Xin Cao Yu Song |
| author_sort | Lidan Xue |
| collection | DOAJ |
| description | Introduction. Along with blood glucose levels, diabetic retinopathy (DR) development also involves endogenous risk factors, such as trimethylamine-N-oxide (TMAO), a product of intestinal flora metabolic disorder, which exacerbates diabetic microvascular complications. However, the effect of TMAO on retinal cells under high-glucose conditions remains unclear. Therefore, this study examined the effects of TMAO on high-glucose-induced retinal dysfunction in the context of NLRP3 inflammasome activation, which is involved in DR. Materials and Methods. TMAO was assessed in the serum and aqueous humor of patients using ELISA. Human retinal microvascular endothelial cells (HRMECs) were treated for 72 h as follows: NG (normal glucose, D-glucose 5.5 mM), NG + TMAO (5 μM), HG (high glucose, D-glucose 30 mM), and HG + TMAO (5 μM). The CCK8 assay was then used to assess cell proliferation; wound healing, cell migration, and tube formation assays were used to verify changes in cell phenotype. ZO-1 expression was determined using immunofluorescence and western blotting. Reactive oxygen species (ROS) formation was assessed using DCFH-DA. NLRP3 inflammasome complex activation was determined using a western blot. Results. The serum and aqueous humor from patients with PDR contained higher levels of TMAO compared to patients with nontype 2 diabetes (Control), non-DR (NDR), and non-PDR (NPDR). TMAO showed significant acceleration of high-glucose-induced cell proliferation, wound healing, cell migration, and tube formation. ZO-1 expression decreased remarkably with the combined action of TMAO and a high glucose compared to either treatment alone. TMAO also promoted high-glucose-activated NLRP3 inflammasome complex. Conclusion. The combination of TMAO and high-glucose results in increased levels of ROS and NLRP3 inflammasome complex activation in HRMECs, leading to exacerbated retinal dysfunction and barrier failure. Thus, TMAO can accelerate PDR occurrence and development, thus indicating the need for early fundus monitoring in diabetic patients with intestinal flora disorders. |
| format | Article |
| id | doaj-art-7b77fdb59d634c58bb7c6d44fbf72978 |
| institution | Kabale University |
| issn | 2090-0058 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Ophthalmology |
| spelling | doaj-art-7b77fdb59d634c58bb7c6d44fbf729782025-02-03T06:47:31ZengWileyJournal of Ophthalmology2090-00582023-01-01202310.1155/2023/8224752Trimethylamine-N-Oxide Promotes High-Glucose-Induced Dysfunction and NLRP3 Inflammasome Activation in Retinal Microvascular Endothelial CellsLidan Xue0Lili Huang1Yajing Tian2Xin Cao3Yu Song4Department of OphthalmologyDepartment of OphthalmologyDepartment of OphthalmologyDepartment of OphthalmologyDepartment of OphthalmologyIntroduction. Along with blood glucose levels, diabetic retinopathy (DR) development also involves endogenous risk factors, such as trimethylamine-N-oxide (TMAO), a product of intestinal flora metabolic disorder, which exacerbates diabetic microvascular complications. However, the effect of TMAO on retinal cells under high-glucose conditions remains unclear. Therefore, this study examined the effects of TMAO on high-glucose-induced retinal dysfunction in the context of NLRP3 inflammasome activation, which is involved in DR. Materials and Methods. TMAO was assessed in the serum and aqueous humor of patients using ELISA. Human retinal microvascular endothelial cells (HRMECs) were treated for 72 h as follows: NG (normal glucose, D-glucose 5.5 mM), NG + TMAO (5 μM), HG (high glucose, D-glucose 30 mM), and HG + TMAO (5 μM). The CCK8 assay was then used to assess cell proliferation; wound healing, cell migration, and tube formation assays were used to verify changes in cell phenotype. ZO-1 expression was determined using immunofluorescence and western blotting. Reactive oxygen species (ROS) formation was assessed using DCFH-DA. NLRP3 inflammasome complex activation was determined using a western blot. Results. The serum and aqueous humor from patients with PDR contained higher levels of TMAO compared to patients with nontype 2 diabetes (Control), non-DR (NDR), and non-PDR (NPDR). TMAO showed significant acceleration of high-glucose-induced cell proliferation, wound healing, cell migration, and tube formation. ZO-1 expression decreased remarkably with the combined action of TMAO and a high glucose compared to either treatment alone. TMAO also promoted high-glucose-activated NLRP3 inflammasome complex. Conclusion. The combination of TMAO and high-glucose results in increased levels of ROS and NLRP3 inflammasome complex activation in HRMECs, leading to exacerbated retinal dysfunction and barrier failure. Thus, TMAO can accelerate PDR occurrence and development, thus indicating the need for early fundus monitoring in diabetic patients with intestinal flora disorders.http://dx.doi.org/10.1155/2023/8224752 |
| spellingShingle | Lidan Xue Lili Huang Yajing Tian Xin Cao Yu Song Trimethylamine-N-Oxide Promotes High-Glucose-Induced Dysfunction and NLRP3 Inflammasome Activation in Retinal Microvascular Endothelial Cells Journal of Ophthalmology |
| title | Trimethylamine-N-Oxide Promotes High-Glucose-Induced Dysfunction and NLRP3 Inflammasome Activation in Retinal Microvascular Endothelial Cells |
| title_full | Trimethylamine-N-Oxide Promotes High-Glucose-Induced Dysfunction and NLRP3 Inflammasome Activation in Retinal Microvascular Endothelial Cells |
| title_fullStr | Trimethylamine-N-Oxide Promotes High-Glucose-Induced Dysfunction and NLRP3 Inflammasome Activation in Retinal Microvascular Endothelial Cells |
| title_full_unstemmed | Trimethylamine-N-Oxide Promotes High-Glucose-Induced Dysfunction and NLRP3 Inflammasome Activation in Retinal Microvascular Endothelial Cells |
| title_short | Trimethylamine-N-Oxide Promotes High-Glucose-Induced Dysfunction and NLRP3 Inflammasome Activation in Retinal Microvascular Endothelial Cells |
| title_sort | trimethylamine n oxide promotes high glucose induced dysfunction and nlrp3 inflammasome activation in retinal microvascular endothelial cells |
| url | http://dx.doi.org/10.1155/2023/8224752 |
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