ArticleThe Journal of clinical investigation2023
Perilipin 2-positive mononuclear phagocytes accumulate in the diabetic retina and promote PPARγ-dependent vasodegeneration.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 19 citations in OpenAlex.
- Review
- Targeting CDH13 as a therapeutic strategy to mitigate pathological ocular angiogenesis.Journal of translational medicine · 2026Article
- Review
- Gut Microbiota, Lipidome, and Metabolites Mediate Immune Dysregulation in Diabetic Microvascular Disease: A Two-sample Mendelian Randomization and Mediation Analysis.Endocrine, metabolic & immune disorders drug targets · 2026Article
- Targeting the gut-retina axis: mechanistic insights and therapeutic prospects for diabetic retinopathy.Inflammopharmacology · 2025Review
- HLA-A drives diabetic retinopathy pathogenesis: multi-omics integration reveals resveratrol's therapeutic potential via immunomodulation.Journal of translational medicine · 2025Article
- Lipid droplet dynamics in type 2 diabetes and its complications: pathophysiological insights and therapeutic options.Lipids in health and disease · 2025Review
- PLIN2 promotes colorectal cancer progression through CD36-mediated epithelial-mesenchymal transition.Cell death & disease · 2025Article
- Plin2 Coordinates Immune and Metabolic Reprogramming in Lacrimal Gland Aging.Investigative ophthalmology & visual science · 2025Article
- Recent Advancements in Understanding the Role and Mechanisms of Angiopoietin-like Proteins in Diabetic Retinopathy.Metabolites · 2025Review
- Chronic intermittent hypoxia disrupts protective microgliosis in ischemic proliferative retinopathy.Journal of neuroinflammation · 2025Article
- Association between Disorders of Lipid Metabolism and Oculopathy: An Overview.International journal of medical sciences · 2025Review
- Identification of novel lipid metabolism-related biomarkers of aortic dissection by integrating single-cell RNA sequencing analysis and machine learning algorithms.Frontiers in immunology · 2025Article
- Multi level effects of Sanghuang Tongxie Formula on type 2 diabetes rats: a comprehensive analysis from intestinal bacteria to metabolome and transcriptome.Frontiers in endocrinology · 2025Article
- Review
- All-trans retinoic acid inhibits glioblastoma progression and attenuates radiation-induced brain injury.JCI insight · 2024Article
- Association Between Systemic Immune Inflammation Index and Diabetes Mellitus in the NHANES 2003-2018 Population.Journal of the Endocrine Society · 2024Article
- Macrophage activation contributes to diabetic retinopathy.Journal of molecular medicine (Berlin, Germany) · 2024Review
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Authors and funding
19 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and dyslipidemia, leads to nonproliferative diabetic retinopathy (NPDR). NPDR is associated with blood-retina barrier disruption, plasma exudates, microvascular degeneration, elevated inflammatory cytokine levels, and monocyte (Mo) infiltration. Whether and how the diabetes-associated changes in plasma lipid and carbohydrate levels modify Mo differentiation remains unknown. Here, we show that mononuclear phagocytes (MPs) in areas of vascular leakage in DR donor retinas expressed perilipin 2 (PLIN2), a marker of intracellular lipid load. Strong upregulation of PLIN2 was also observed when healthy donor Mos were treated with plasma from patients with T2DM or with palmitate concentrations typical of those found in T2DM plasma, but not under high-glucose conditions. PLIN2 expression correlated with the expression of other key genes involved in lipid metabolism (ACADVL, PDK4) and the DR biomarkers ANGPTL4 and CXCL8. Mechanistically, we show that lipid-exposed MPs induced capillary degeneration in ex vivo explants that was inhibited by pharmaceutical inhibition of PPARγ signaling. Our study reveals a mechanism linking dyslipidemia-induced MP polarization to the increased inflammatory cytokine levels and microvascular degeneration that characterize NPDR. This study provides comprehensive insights into the glycemia-independent activation of Mos in T2DM and identifies MP PPARγ as a target for inhibition of lipid-activated MPs in DR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.