Müller cells harboring exosomal lncRNA OGRU modulates microglia polarization in diabetic retinopathy via serving as miRNA sponges DOI
ShuHua Fu, Wenjing Sun, Lu Liu

et al.

Diabetes, Journal Year: 2024, Volume and Issue: 73(11), P. 1919 - 1934

Published: Aug. 23, 2024

Diabetic retinopathy (DR) is one of the most common complications diabetes worldwide and associated with visual loss blindness. However, effective treatments for both early- late-stage DR remain lacking. A streptozotocin-induced diabetic mouse model high glucose (HG)–treated Müller cell were established. M1/M2 microglia polarization was assessed by immunofluorescence staining flow cytometry. Expression long noncoding RNA (lncRNA) OGRU, cytokines, other key molecules detected quantitative RT-PCR or Western blot. ELISA used to monitor cytokine secretion. cell–derived exosomes isolated characterized nanopartical tracking analysis, blot, transmission electron microscopy, exosome uptake assay intercellular transport exosomes. Associations among lncRNA-miRNA-mRNA networks validated pulldown immunoprecipitation dual luciferase assays. Increased M1 but decreased M2 retinal observed in mice. HG-treated transported OGRU into promoted toward phenotype. Mechanistically, served as a competing endogenous miR-320-3p, miR-221-3p, miR-574-5p regulate aldose reductase (AR), PFKFB3, transporter 1 (GLUT1) expression microglia, respectively. Loss miR-320-3p/miR-221-3p/miR-574-5p reinforced AR/PFKFB3/GLUT1 abrogated silencing–mediated vitro. In vivo studies further showed that OGRU/miR-320-3p/AR, OGRU/miR-221-3p/PFKFB3, OGRU/miR-574-5p/GLUT1 axes regulated Collectively, exosomal modulating axes. Article Highlights

Language: Английский

Endothelial progenitor cells as biomarkers of diabetes-related cardiovascular complications DOI Creative Commons

Josefa Benítez-Camacho,

Antonio Ballesteros, Lucía Beltrán-Camacho

et al.

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 10, 2023

Abstract Diabetes mellitus (DM) constitutes a chronic metabolic disease characterized by elevated levels of blood glucose which can also lead to the so-called diabetic vascular complications (DVCs), responsible for most morbidity, hospitalizations and death registered in these patients. Currently, different approaches prevent or reduce DM its DVCs have focused on reducing sugar levels, cholesterol management even changes lifestyle habits. However, strictest glycaemic control strategies are not always sufficient development DVCs, reflects need identify reliable biomarkers capable predicting further Endothelial progenitor cells (EPCs), widely known their potential applications cell therapy due regenerative properties, may be used as differential markers considering that number functionality affected under pathological environments related DM. Besides, drugs commonly with patients influence level behaviour EPCs pleiotropic effect could finally decisive prognosis disease. In current review, we analysed relationship between diabetes focusing use progression towards major complications. Moreover, effects function been addressed. Graphical

Language: Английский

Citations

7

Deciphering Müller cell heterogeneity signatures in diabetic retinopathy across species: an integrative single-cell analysis DOI Creative Commons

Xiyuan Deng,

Ya Mo,

Xiuying Zhu

et al.

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: May 3, 2024

Diabetic retinopathy (DR), a leading cause of visual impairment, demands profound comprehension its cellular mechanisms to formulate effective therapeutic strategies. Our study presentes comprehensive single-cell analysis elucidating the intricate landscape Müller cells within DR, emphasizing their nuanced involvement. Utilizing scRNA-seq data from both Sprague-Dawley rat models and human patients, we delineated distinct cell clusters corresponding gene expression profiles. These findings were further validated through differential utilizing transcriptomic data. Notably, certain displayed upregulation Rho gene, implying phagocytic response damaged photoreceptors DR microenvironment. This phenomenon was consistently observed across species. Additionally, co-expression patterns RHO PDE6G provided compelling evidence supporting potential role in maintaining retinal integrity during DR. results offer novel insights into dynamics underscore as promising targets for preserving vision disorders induced by diabetes.

Language: Английский

Citations

2

The role of pericyte in ocular vascular diseases DOI Open Access

Lianjun Shi,

Huimin Ge,

Fan Ye

et al.

Journal of Biomedical Research, Journal Year: 2024, Volume and Issue: 38(6), P. 521 - 521

Published: Jan. 1, 2024

Pericytes are located in the stromal membrane of capillary outer wall and contain endothelial cells (ECs). They pivotal regulating blood flow, enhancing vascular stability, maintaining integrity blood-retina barrier (BRB)/blood-brain (BBB). The pluripotency pericytes allows them to differentiate into various cell types, highlighting their significance disease pathogenesis, as demonstrated by previous studies. This potential enables be a biomarker for diagnosis target treatment disorders. retina, an essential part eyeball, is extension cerebral tissue with transparent refractive medium. It offers unique window assessing systemic microvascular lesions. Routine fundus examination necessary patients diabetes hypertension. Manifestations, such retinal artery tortuosity, dilation, stenosis, abnormal arteriovenous anastomosis, serve typical hallmarks vasculopathy. Therefore, studies ocular diseases significantly facilitate exploration diseases.

Language: Английский

Citations

2

Role of inflammation in diabetic macular edema and neovascular age-related macular degeneration DOI Creative Commons
Stela Vujosevic, Marco Lupidi, Simone Donati

et al.

Survey of Ophthalmology, Journal Year: 2024, Volume and Issue: 69(6), P. 870 - 881

Published: July 18, 2024

Diabetic macular edema (DME) and neovascular age-related degeneration (nAMD) are multifactorial disorders that affect the macula cause significant vision loss. Although inflammation neoangiogenesis hallmarks of DME nAMD, respectively, they share some biochemical mediators. While is a trigger for processes lead to development DME, in nAMD seems be consequence retinal pigment epithelium Bruch membrane alterations. These pathophysiologic differences may key issue justifies difference treatment strategies. Vascular endothelial growth factor inhibitors have changed both diseases, however, many patients with fail achieve established therapeutic goals. From clinical perspective, targeting inflammatory pathways intravitreal corticosteroids has been proven effective DME. On contrary, relevance addressing not yet. We explore role implication its therapeutical relevance.

Language: Английский

Citations

2

Müller cells harboring exosomal lncRNA OGRU modulates microglia polarization in diabetic retinopathy via serving as miRNA sponges DOI
ShuHua Fu, Wenjing Sun, Lu Liu

et al.

Diabetes, Journal Year: 2024, Volume and Issue: 73(11), P. 1919 - 1934

Published: Aug. 23, 2024

Diabetic retinopathy (DR) is one of the most common complications diabetes worldwide and associated with visual loss blindness. However, effective treatments for both early- late-stage DR remain lacking. A streptozotocin-induced diabetic mouse model high glucose (HG)–treated Müller cell were established. M1/M2 microglia polarization was assessed by immunofluorescence staining flow cytometry. Expression long noncoding RNA (lncRNA) OGRU, cytokines, other key molecules detected quantitative RT-PCR or Western blot. ELISA used to monitor cytokine secretion. cell–derived exosomes isolated characterized nanopartical tracking analysis, blot, transmission electron microscopy, exosome uptake assay intercellular transport exosomes. Associations among lncRNA-miRNA-mRNA networks validated pulldown immunoprecipitation dual luciferase assays. Increased M1 but decreased M2 retinal observed in mice. HG-treated transported OGRU into promoted toward phenotype. Mechanistically, served as a competing endogenous miR-320-3p, miR-221-3p, miR-574-5p regulate aldose reductase (AR), PFKFB3, transporter 1 (GLUT1) expression microglia, respectively. Loss miR-320-3p/miR-221-3p/miR-574-5p reinforced AR/PFKFB3/GLUT1 abrogated silencing–mediated vitro. In vivo studies further showed that OGRU/miR-320-3p/AR, OGRU/miR-221-3p/PFKFB3, OGRU/miR-574-5p/GLUT1 axes regulated Collectively, exosomal modulating axes. Article Highlights

Language: Английский

Citations

2