ArticleInvestigative ophthalmology & visual science2014
Modulation of VEGF-induced retinal vascular permeability by peroxisome proliferator-activated receptor-β/δ.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 43 citations in OpenAlex.
- Synergistic inhibition of macular vascular permeability in diabetic edema: Ginsenoside Rg3 enhances ranibizumab efficacy by targeting angiopoietin-like protein 4 and vascular endothelial growth factor via neuropilin/RhoA signaling.Journal of diabetes investigation · 2026Article
- Faricimab Reverts VEGF-AInternational journal of molecular sciences · 2025Article
- Review
- Cathepsin S Knockdown Suppresses Endothelial Inflammation, Angiogenesis, and Complement Protein Activity under Hyperglycemic Conditions In Vitro by Inhibiting NF-κB Signaling.International journal of molecular sciences · 2023Article
- Beovu, but not Lucentis impairs the function of the barrier formed by retinal endothelial cells in vitro.Scientific reports · 2022Article
- RNA-Seq Provides Insights into VEGF-Induced Signaling in Human Retinal Microvascular Endothelial Cells: Implications in Retinopathy of Prematurity.International journal of molecular sciences · 2022Article
- Endothelial Cell Transcytosis Assay as an In Vitro Model to Evaluate Inner Blood-Retinal Barrier Permeability.Journal of visualized experiments : JoVE · 2022Article
- Impairment of the Retinal Endothelial Cell Barrier Induced by Long-Term Treatment with VEGF-ABiomolecules · 2022Article
- Endothelial PPARδ facilitates the post-ischemic vascular repair through interaction with HIF1α.Theranostics · 2022Article
- Therapeutic Effects of Fenofibrate Nano-Emulsion Eye Drops on Retinal Vascular Leakage and Neovascularization.Biology · 2021Article
- The role of peroxisome proliferator-activated receptors in healthy and diseased eyes.Experimental eye research · 2021Review
- Article
- Evans blue staining to detect deep blood vessels in peripheral retina for observing retinal pathology in early-stage diabetic rats.International journal of ophthalmology · 2021Article
- Small-Molecule Modulation of PPARs for the Treatment of Prevalent Vascular Retinal Diseases.International journal of molecular sciences · 2020Review
- Investigating the Role of PPARβ/δ in Retinal Vascular Remodeling UsingInternational journal of molecular sciences · 2020Article
- Long-Acting FGF21 Inhibits Retinal Vascular Leakage in In Vivo and In Vitro Models.International journal of molecular sciences · 2020Article
- Sitagliptin and the Blood-Retina Barrier: Effects on Retinal Endothelial Cells Manifested Only after Prolonged Exposure.Journal of diabetes research · 2020Article
- PPARInternational journal of hypertension · 2019Review
- Palmitic Acid Induces Müller Cell Inflammation that is Potentiated by Co-treatment with Glucose.Scientific reports · 2018Article
- Selection of Reference Genes for Studies of Human Retinal Endothelial Cell Gene Expression by Reverse Transcription-Quantitative Real-Time Polymerase Chain Reaction.Gene reports · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeVascular endothelial growth factor (VEGF)-induced retinal vascular permeability contributes to diabetic macular edema (DME), a serious vision-threatening condition. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) antagonist/reverse agonist, GSK0660, inhibits VEGF-induced human retinal microvascular endothelial cell (HRMEC) proliferation, tubulogenesis, and oxygen-induced retinal vasculopathy in newborn rats. These VEGF-induced HRMEC behaviors and VEGF-induced disruption of endothelial cell junctional complexes may well share molecular signaling events. Thus, we sought to examine the role of PPARβ/δ in VEGF-induced retinal hyperpermeability.
methodsTransendothelial electrical resistance (TEER) measurements were performed on HRMEC monolayers to assess permeability. Claudin-1/Claudin-5 localization in HRMEC monolayers was determined by immunocytochemistry. Extracellular signal-regulated protein kinases 1 and 2 (Erk 1/2) phosphorylation, VEGF receptor 1 (VEGFR1) and R2 were assayed by Western blot analysis. Expression of VEGFR1 and R2 was measured by quantitative RT-PCR. Last, retinal vascular permeability was assayed in vivo by Evans blue extravasation.
resultsHuman retinal microvascular endothelial cell monolayers treated with VEGF for 24 hours showed decreased TEER values that were completely reversed by the highest concentration of GSK0660 (10 μM) and PPARβ/δ-directed siRNA (20 μM). In HRMEC treated with VEGF, GSK0660 stabilized tight-junctions as evidenced by Claudin-1 staining, reduced phosphorylation of Erk1/2, and reduced VEGFR1/2 expression. Peroxisome proliferator-activated receptor β/δ siRNA had a similar effect on VEGFR expression and Claudin-1, supporting the specificity of GSK0660 in our experiments. Last, GSK0660 significantly inhibited VEGF-induced retinal vascular permeability and reduced retinal VEGFR1and R2 levels in C57BL/6 mice.
conclusionsThese data suggest a protective effect for PPARβ/δ antagonism against VEGF-induced vascular permeability, possibly through reduced VEGFR expression. Therefore, antagonism/reverse agonism of PPARβ/δ siRNA may represent a novel therapeutic methodology against retinal hyperpermeability and is worthy of future investigation.
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.