Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions

MedComm, Journal Year: 2024, Volume and Issue: 5(4)

Published: April 1, 2024

Abstract At present, diabetes mellitus (DM) has been one of the most endangering healthy diseases. Current therapies contain controlling high blood sugar, reducing risk factors like obesity, hypertension, and so on; however, DM patients inevitably eventually progress into different types complications, resulting in poor quality life. Unfortunately, clear etiology pathogenesis complications have not elucidated owing to intricate whole‐body systems. The immune system was responsible regulate homeostasis by triggering or resolving inflammatory response, indicating it may be necessary complications. In fact, previous studies shown inflammation plays multifunctional roles is attracting attention meaningful therapeutic strategy. To this end, review systematically concluded current over relationships susceptible (e.g., diabetic cardiomyopathy, retinopathy, peripheral neuropathy, nephropathy) inflammation, ranging from cell cytokines interaction pathomechanism organ injury. Besides, we also summarized various strategies improve target special remedies conventional lifestyle changes. This will offer a panoramic insight mechanisms an perspective discuss contemporary clinical interventions.

Language: Английский

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Retinopathy of Prematurity and MicroRNAs

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 400 - 400

Published: Feb. 7, 2025

Retinopathy of Prematurity (ROP), a leading cause blindness in preterm infants, arises from dysregulated angiogenesis and inflammation. Without timely intervention, ROP can progress to severe outcomes, including dense fibrovascular plaques retinal detachment. MicroRNAs (miRNAs) regulate key pathways such as hypoxia response, VEGF signaling, vascular remodeling. Studies have identified miRNAs (e.g., miR-210, miR-146a, miR-21) potential biomarkers therapeutic targets. Preclinical evidence supports miRNA-based therapies miR-18a-5p miR-181a), targeting HIF-1α VEGFA mitigate neovascularization, with nanoparticle delivery systems enhancing stability specificity. These strategies, combined anti-VEGF agents, show significant for improving management. While promising, miRNA require validation clinical trials ensure safety efficacy. This review discusses the role ROP, highlighting their relevance diagnostic tools.

Language: Английский

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Microvascular destabilization and intricated network of the cytokines in diabetic retinopathy: from the perspective of cellular and molecular components

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 27, 2024

Microvascular destabilization is the primary cause of inner blood-retinal barrier (iBRB) breakdown and increased vascular leakage in diabetic retinopathy (DR). results from combinational effects levels growth factors cytokines, involvement inflammation, changed cell-to-cell interactions, especially loss endothelial cells pericytes, due to hyperglycemia hypoxia. As manifestation microvascular destabilization, fluid transports via paracellular transcellular routes increase disruption intercellular junctional complexes and/or altered caveolar transport across retinal endothelium. With diabetes progression, functional structural changes iBRB components, including cellular noncellular further facilitate aggravate resulting macular edema, neuroretinal damage dysfunction neurovascular unit (iNVU). Although there have been considerable recent advances towards a better understanding complex molecular network underlying some still remain be fully elucidated. Recent data indicate that targeting intricate signaling pathways may allow against destabilization. Therefore, efforts made clarify mechanisms are involved DR. In this review, we discuss: (1) brief introduction DR destabilization; (2) components iNVU, iBRB; (3) matrix contacts maintain stabilization, glycocalyx, basement membrane, various cell-cell interactions; (4) mediated cell death; (5) cytokines as well This comprehensive review aimed provide insights for by key molecules or specific cells, thus restoring function structure treat

Language: Английский

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New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases

Journal of Histochemistry & Cytochemistry, Journal Year: 2024, Volume and Issue: 72(5), P. 329 - 352

Published: May 1, 2024

Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate glycolysis. In fact, all cells, both non-cancer cancer need for biosynthesis building blocks cell growth tissue expansion. Moreover, non-proliferating stem tumors leader tip ECs during rely on glycolysis pyruvate production, which used synthesis mitochondria through oxidative phosphorylation (OXPHOS). Therefore, not specific but rather limits its utility therapy. However, local treatment angiogenic eye conditions with inhibitors may be safe therapeutic option that warrants experimental investigation. Most types such as photoreceptors pericytes use OXPHOS whereas production. (J Histochem Cytochem XX.XXX–XXX, XXXX)

Language: Английский

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Neurovascular Relationships in AGEs-Based Models of Proliferative Diabetic Retinopathy

Bioengineering, Journal Year: 2024, Volume and Issue: 11(1), P. 63 - 63

Published: Jan. 8, 2024

Diabetic retinopathy affects more than 100 million people worldwide and is projected to increase by 50% within 20 years. Increased blood glucose leads the formation of advanced glycation end products (AGEs), which cause cellular molecular dysfunction across neurovascular systems. These molecules initiate slow breakdown retinal vasculature inner barrier (iBRB), resulting in ischemia abnormal angiogenesis. This project examined impact AGEs altering morphology healthy cells that comprise iBRB, as well effects on thrombi formation, vitro. Our results illustrate significantly alter areas clots via elevated levels tissue factor. Likewise, upregulate expression cell receptors (RAGE) both endothelial glial cells, a hallmark biomarker inflammation diabetic cells. Examining stimulation functions work diminish iBRB integrity will greatly help advance therapies target vision loss adults.

Language: Английский

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Agonism of β3-Adrenoceptors Inhibits Pathological Retinal Angiogenesis in the Model of Oxygen-Induced Retinopathy

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(10), P. 34 - 34

Published: Aug. 26, 2024

Purpose: In response to hypoxia, sympathetic fibers the retina activate β-adrenoceptors (β-ARs) that play an important role in regulation of vascular and neuronal functions. We investigated β3-AR using mouse model oxygen-induced retinopathy (OIR). Methods: Mouse pups were exposed 75% oxygen at postnatal day 7 (PD7) followed by a return room air PD12. The preferential agonist BRL37344 was subcutaneously administered once daily different times after air. At PD17, OIR mice underwent flash pattern electroretinogram. After sacrifice, retinal wholemounts used for vessel staining or immunohistochemistry astrocytes, Müller cells, ganglion cells (RGCs). homogenates, levels markers associated with neovascularization (NV), blood–retinal barrier (BRB), astrocytes determined western blot, quantitative reverse-transcription polymerase chain reaction assess messenger. Administration antagonist SR59230A performed verify selectivity. Results: expression is upregulated but its increase prevented BRL37344, which counteracts NV inhibiting pro-angiogenic pathway, activating anti-angiogenic recovering BRB-associated markers, triggering nitric oxide production, favoring revascularization central through recovered density ultimately midperiphery. Vasculature rescue prevents dysfunctional activity OIR-associated cell loss. Conclusions: has emerged as crucial intermediary hypoxia-dependent NV, suggesting agonists treatment proliferative retinopathies.

Language: Английский

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IOP-induced blood-retinal barrier compromise contributes to RGC death in glaucoma

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 18, 2024

The integrity of the blood-retinal barrier (BRB) has been largely unexplored in glaucoma. We reveal that elevated intraocular pressure (IOP) partially compromises BRB two human-relevant inherited mouse models glaucoma (DBA/2J and Lmx1bV265D). Experimentally increasing IOP eyes further confirms this. Notably, compromise induces subtle leakage, happening without bleeding or detected endothelial cell junction disruption, it precedes neurodegeneration. Leakage occurs from peripheral veins retinal ganglion layer with a concomitant loss transcytosis inhibitor MFSD2A. Importantly, stabilizing β-catenin cells prevents both vascular leakage neurodegeneration DBA/2J model. occurrence all 3 high indicates may be common, yet overlooked, mechanism These findings suggest IOP-induced plays critical role glaucoma, offering new therapeutic target.

Language: Английский

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ADAMTS13 Improves Endothelial Function and Reduces Inflammation in Diabetic Retinopathy

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 85 - 85

Published: Jan. 9, 2025

The protease, a disintegrin and metalloproteinase with thrombospondin type 1 motif member 13 (ADAMTS13), known to cleave only the von Willebrand factor (VWF), has powerful regulatory effects on microvascular platelet adhesion, thrombosis, inflammation, endothelial dysfunction. We study protection against diabetes-induced retinal injury in experimental rats by supplementation recombinant ADAMTS13. compare human epiretinal membranes vitreous samples from nondiabetic subjects patients proliferative diabetic retinopathy (PDR) extend vitro analyses use of various immunodetection spectrofluorimetric methods rat retina glial cell cultures. Functional studies include assessment blood–retinal barrier (BRB), angiogenesis. In membranes, cells monocytes/macrophages express levels VWF, marker CD41, ADAMTS13, biomarkers soluble VE-cadherin syndecan-1 are increased PDR vitreous. ADAMTS13 is downregulated retinas. intravitreal administration attenuates BRB breakdown, downregulation β-catenin, upregulation phospho-ERK1/2, HMGB1, VCAM-1, ICAM-1. Müller cells, MCP-1, MMP-9, ROS induced mimetic conditions. HRMECs, shedding fractalkine, conditions, ICAM-1 VCAM-1 elicited TNF-α, adherence monocytes VEGF-induced migration cells. Our findings suggest that enhancing situ ameliorates inflammation vascular

Language: Английский

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Exploring Endothelial Cell Dysfunction’s Impact on the Brain-Retina Microenvironment Connection: Molecular Mechanisms and Implications

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Language: Английский

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Retinal physiology in metabolic syndrome

Advances in genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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