A single cell atlas of circulating immune cells involved in diabetic retinopathy

iScience, Journal Year: 2024, Volume and Issue: 27(2), P. 109003 - 109003

Published: Jan. 26, 2024

This study focused on examining the exact role of circulating immune cells in development diabetic retinopathy (DR). In vitro co-culture experiments showed that peripheral blood mononuclear (PBMCs) from patients with type 1 DR crucially modulated biological functions human retinal microvascular endothelial (HRMECs), consequently disrupting their normal functionality. Single-cell RNA sequencing (scRNA-seq) revealed unique differentially expressed genes and pathways among healthy controls, non-diabetic (NDR) patients, patients. Of significance was observed upregulation JUND each subset PBMCs DR. Further studies downregulating patient-derived led to amelioration HRMEC dysfunction. These findings highlighted notable alterations transcriptomic patterns underscored as a key factor for participating pathogenesis

Language: Английский

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Single-cell RNA sequencing reveals roles of unique retinal microglia types in early diabetic retinopathy

Diabetology & Metabolic Syndrome, Journal Year: 2024, Volume and Issue: 16(1)

Published: Feb. 26, 2024

The pathophysiological mechanisms of diabetic retinopathy (DR), a blinding disease, are intricate. DR was thought to be microvascular disease previously. However, growing studies have indicated that the retinal microglia-induced inflammation precedes microangiopathy. binary concept microglial M1/M2 polarization paradigms during inflammatory activation has been debated. In this study, we confirmed microglia had most significant changes in early using single-cell RNA sequencing. A total five specimens were collected from donor SD rats. Changes various cells retina at stage analyzed sequencing technology. We defined three new subtypes cellular level, including two M1 types (Egr2+ and Egr2- M1) one M2 type. also revealed anatomical location between these subtypes, dynamic phenotypes, possible sequence mutual regulatory mechanism different cells. Furthermore, constructed an network involving microglia, blood-derived macrophages other nonneuronal targeted study disease-specific can shorten time for drug screening clinical application, which provided insight control reversal DR. found show obvious differential expression reveal high-glucose microenvironment level. Our comprehensive analysis will help achieve occurrence progression

Language: Английский

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Long noncoding RNA MIAT regulates primary human retinal pericyte pyroptosis by modulating miR-342–3p targeting of CASP1 in diabetic retinopathy

Experimental Eye Research, Journal Year: 2020, Volume and Issue: 202, P. 108300 - 108300

Published: Oct. 13, 2020

Language: Английский

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Differences in Biomarkers of Inflammation Between Novel Subgroups of Recent-Onset Diabetes

Diabetes, Journal Year: 2021, Volume and Issue: 70(5), P. 1198 - 1208

Published: Feb. 19, 2021

A novel clustering approach identified five subgroups of diabetes with distinct progression trajectories complications. We hypothesized that these differ in multiple biomarkers inflammation. Serum levels 74 inflammation were measured 414 individuals recent adult-onset from the German Diabetes Study (GDS) allocated to based on data-driven cluster analysis. Pairwise differences between for assessed generalized linear mixed models before (model 1) and after 2) adjustment variables. Participants assigned subgroups: severe autoimmune (21%), insulin-deficient (SIDD) (3%), insulin-resistant (SIRD) (9%), mild obesity-related (32%), age-related (35%). In model 1, 23 showed one or more pairwise (Bonferroni-corrected P < 0.0007). Biomarker generally highest SIRD lowest SIDD. All correlated 2, three (CASP-8, EN-RAGE, IL-6) at least difference (e.g., lower CASP8, IL-6 SIDD vs. all other subgroups, Thus, show inflammation, underlining a prominent role inflammatory pathways particular SIRD.

Language: Английский

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Targeting Inflammatory Cytokines to Improve Type 2 Diabetes Control

BioMed Research International, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 12

Published: Sept. 13, 2021

Type 2 diabetes (T2D) is one of the most common chronic metabolic disorders in adulthood worldwide, whose pathophysiology includes an abnormal immune response accompanied by cytokine dysregulation and inflammation. As T2D-related inflammation its progression were associated with balance between pro anti-inflammatory cytokines, anticytokine treatments might represent additional therapeutic option for T2D patients. This review focuses on existing evidence antihyperglycemic properties disease-modifying antirheumatic drugs (DMARDs) agents (anti-TNF-α, anti-interleukin-(IL-) 6, -IL-1, -IL-17, -IL-23, etc.). Emphasis placed their molecular mechanisms biological rationale clinical use. Finally, we briefly summarize results from experimental model studies promising trials about potential therapies T2D, discussing effects these systemic islet inflammation, beta-cell function, insulin secretion, sensitivity.

Language: Английский

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Pyroptosis in the Retinal Neurovascular Unit: New Insights Into Diabetic Retinopathy

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 19, 2021

Diabetic retinopathy (DR) is prevalent among people with long-term diabetes mellitus (DM) and remains the leading cause of visual impairment in working-aged people. DR related to chronic low-level inflammatory reactions. Pyroptosis an emerging type cell death mediated by gasdermin D (GSDMD), NOD-like receptors caspases that promote interleukin-1β (IL-1β) IL-18 release. In addition, retinal neurovascular unit (NVU) functional basis retina. Recent studies have shown pyroptosis may participate destruction NVU cells simulated hyperglycemic environments. this review, we will clarify importance during development DR.

Language: Английский

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Microneedle-based ocular drug delivery systems – recent advances and challenges

Beilstein Journal of Nanotechnology, Journal Year: 2022, Volume and Issue: 13, P. 1167 - 1184

Published: Oct. 24, 2022

Eye diseases and injuries constitute a significant clinical problem worldwide. Safe effective delivery of drugs to the eye is challenging mostly due presence ocular barriers clearance mechanisms. In everyday practice, traditional drops, gels ointments are most often used. Unfortunately, they usually not well tolerated by patients need for frequent use as discomfort during application. Therefore, novel drug systems with improved biopharmaceutical properties subject ongoing scientific investigations. Due developments in microtechnology, recent years, there has been remarkable advance development microneedle-based an alternative, non-invasive form administering eye. This review summarizes latest achievements field obtaining microneedle patches. manuscript, important manufacturing technologies, classification, research studies related ophthalmic application microneedles presented. Finally, advantages drawbacks, potential challenges unique anatomy physiology summarized discussed.

Language: Английский

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Chlorogenic acid improves diabetic retinopathy by alleviating blood‐retinal‐barrier dysfunction via inducing Nrf2 activation

Phytotherapy Research, Journal Year: 2022, Volume and Issue: 36(3), P. 1386 - 1401

Published: Feb. 8, 2022

As one of the major diabetic microvascular complications, retinopathy (DR) is mainly initiated by blood-retinal barrier (BRB) dysfunction. Chlorogenic acid (CGA) a natural polyphenolic compound in Lonicerae Japonicae Flos, which traditionally has beneficial function for eyes and commonly included many anti-diabetic formulas. In this study, potential protective mechanism CGA against DR was investigated. Streptozotocin (STZ) used to induce diabetes mice. attenuated BRB dysfunction reversed endothelial-mesenchymal transition (EndoMT) epithelial-mesenchymal (EMT) retinas vivo. inhibited microglia activation reduced tumor necrosis factor (TNF)α release both vivo vitro. promoted nuclear erythroid 2-related 2 (Nrf2) prevented EndoMT/EMT TNFα-treated human retinal endothelial cells (HRECs) or pigment epithelial APRE19 cells. alleviated endothelial/epithelial oxidative injury HRECs stimulated with TNFα, but effect disappeared co-incubated Nrf2 inhibitor. Additionally, CGA-supplied alleviation on damage markedly weakened from STZ-treated knock-out All results suggest that improves through attenuating reducing microglia-initiated inflammation preventing TNFα-induced via inducing activation.

Language: Английский

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Inflammation and aging-related disease: A transdisciplinary inflammaging framework

GeroScience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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Vitamin D Protects against Oxidative Stress and Inflammation in Human Retinal Cells

Antioxidants, Journal Year: 2020, Volume and Issue: 9(9), P. 838 - 838

Published: Sept. 8, 2020

Diabetic retinopathy is a vision-threatening microvascular complication of diabetes and one the leading causes blindness. Oxidative stress inflammation play major role in its pathogenesis, new therapies counteracting these contributors could be great interest. In current study, we investigated vitamin D against oxidative human retinal pigment epithelium (RPE) endothelial cell lines. We demonstrate that effectively counteracts induced by hydrogen peroxide (H2O2). addition, increased levels proinflammatory proteins such as Interleukin (IL)-6, IL-8, Monocyte chemoattractant protein (MCP)-1, Interferon (IFN)-γ, tumor necrosis factor (TNF)-α triggered lipopolysaccharide (LPS) exposure were significantly decreased addition. Interestingly, IL-18 only addition cells but not RPE cells, suggesting main antiangiogenic under inflammatory conditions. Moreover, H2O2 LPS alteration morphological damage tight junctions adult (ARPE-19) restored conditions to media. conclusion, our data suggest protect retina enhancing antioxidant defense through exhibiting anti-inflammatory properties.

Language: Английский

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