ArticleProceedings of the National Academy of Sciences of the United States of America2019
NOTCH1 signaling induces pathological vascular permeability in diabetic retinopathy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 87 citations in OpenAlex.
- Review
- A noncanonical role for Jagged1 in endothelial mechanotransduction.The FEBS journal · 2026Article
- Models of hyperglycaemia in diabetes mellitus and its complications.Nature reviews. Endocrinology · 2026Review
- Growth Differentiation Factor-15 as a Biomarker of Diabetic Complications in Patients with Type 2 Diabetes.Journal of clinical medicine · 2026Article
- Multimodal AI fuses proteomic and EHR data for rational prioritization of protein biomarkers in diabetic retinopathy.medRxiv : the preprint server for health sciences · 2026Article
- Paracrine signaling mediators of vascular endothelial barrier dysfunction in sepsis: implications for therapeutic targeting.Tissue barriers · 2026Article
- CD36 Regulates PANoptosis in Diabetic Retinopathy via the NOTCH/MAML Pathway.Journal of diabetes research · 2026Article
- Phenotype-driven management of diabetic macular edema: multimodal imaging biomarkers and individualized therapy.Frontiers in medicine · 2026Review
- Matrix stiffness induces endothelial network senescence.bioRxiv : the preprint server for biology · 2025Article
- Comparative Tear Fluid Proteomics to Explore Treatment Responsiveness in Diabetic Macular Edema: A Pilot Study.Journal of proteome research · 2025Article
- Potential mechanisms of epigenetic regulation in diabetic retinopathy from the perspectives of multi-omics.Diabetology & metabolic syndrome · 2025Article
- Multifaceted Role of Notch Signaling in Vascular Health and Diseases.Biomedicines · 2025Review
- The impact of diabetes mellitus on blood-tissue barrier regulation and vascular complications: Is the lung different from other organs?Tissue barriers · 2025Review
- Molecular and Cellular Mechanisms Involved in the Pathophysiology of Retinal Vascular Disease-Interplay Between Inflammation and Oxidative Stress.International journal of molecular sciences · 2024Review
- Potential Drug Targets for Diabetic Retinopathy Identified Through Mendelian Randomization Analysis.Translational vision science & technology · 2024Article
- Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors in Diabetic Retinopathy: An Attractive but Elusive Choice for Drug Development.Pharmaceutics · 2024Review
- Downregulation of hsa-miR-100-5p May Be a Protective Factor in the Early Stages of Nephropathy in Type 1 Diabetes Mellitus.International journal of molecular sciences · 2024Article
- Comparison of Glutathione Nanoparticles, CoEnzyme Q10, and Fish Oil for Prevention of Oxygen-Induced Retinopathy in Neonatal Rats.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Requirement of Site-Specific Tyrosine Phosphorylation of Cortactin in Retinal Neovascularization and Vascular Leakage.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results.Nature medicine · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
Diabetic macular edema is a major complication of diabetes resulting in loss of central vision. Although heightened vessel leakiness has been linked to glial and neuronal-derived factors, relatively little is known on the mechanisms by which mature endothelial cells exit from a quiescent state and compromise barrier function. Here we report that endothelial NOTCH1 signaling in mature diabetic retinas contributes to increased vascular permeability. By providing both human and mouse data, we show that NOTCH1 ligands JAGGED1 and DELTA LIKE-4 are up-regulated secondary to hyperglycemia and activate both canonical and rapid noncanonical NOTCH1 pathways that ultimately disrupt endothelial adherens junctions in diabetic retinas by causing dissociation of vascular endothelial-cadherin from β-catenin. We further demonstrate that neutralization of NOTCH1 ligands prevents diabetes-induced retinal edema. Collectively, these results identify a fundamental process in diabetes-mediated vascular permeability and provide translational rational for targeting the NOTCH pathway (primarily JAGGED1) in conditions characterized by compromised vascular barrier function.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.