ArticleInvestigative ophthalmology & visual science2011
Upregulation of CCR3 by age-related stresses promotes choroidal endothelial cell migration via VEGF-dependent and -independent signaling.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Aqueous humour cytokine profiles in retinal vein occlusion: a comparative study of acute, chronic recurrent, and control eyes.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Circulating Inflammatory Proteins and Age-related Macular Degeneration: New Insights from Mendelian Randomization.Combinatorial chemistry & high throughput screening · 2026Article
- Repurposing lapatinib as a triple antagonist of chemokine receptors 3, 4, and 5.Molecular pharmacology · 2025Article
- The differential proteomic response to ischemic stroke in appalachian subjects treated with mechanical thrombectomy.Journal of neuroinflammation · 2024Observational
- CCL11 released by GSDMD-mediated macrophage pyroptosis regulates angiogenesis after hindlimb ischemia.Cell death discovery · 2024Article
- CCR3 Expression in Relation to Delayed Microbleeds in a Rat Model of Large Vessel Occlusion.Journal of experimental neurology · 2024Article
- Next-generation Tumor-homing Induced Neural Stem Cells as an Adjuvant to Radiation for the Treatment of Metastatic Lung Cancer.Stem cell reviews and reports · 2022Article
- Review
- Age-related macular degeneration.Nature reviews. Disease primers · 2021Review
- IQGAP1 causes choroidal neovascularization by sustaining VEGFR2-mediated Rac1 activation.Angiogenesis · 2020Article
- Erythropoietin Signaling Increases Choroidal Macrophages and Cytokine Expression, and Exacerbates Choroidal Neovascularization.Scientific reports · 2018Article
- CCR3 Is Associated with the Death of a Photoreceptor Cell-line Induced by Light Exposure.Frontiers in pharmacology · 2017Article
- Aqueous cytokine levels are associated with reduced macular thickness after intravitreal ranibizumab for diabetic macular edema.PloS one · 2017Article
- Thy-1 Regulates VEGF-Mediated Choroidal Endothelial Cell Activation and Migration: Implications in Neovascular Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2016Article
- The Age of Cortical Neural Networks Affects Their Interactions with Magnetic Nanoparticles.Small (Weinheim an der Bergstrasse, Germany) · 2016Article
- Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model of Choroidal Neovascularization.PloS one · 2016Article
- AMD Genetics in India: The Missing Links.Frontiers in aging neuroscience · 2016Review
- Regulation of signaling events involved in the pathophysiology of neovascular AMD.Molecular vision · 2016Review
- Rap1 GTPase Inhibits Tumor Necrosis Factor-α-Induced Choroidal Endothelial Migration via NADPH Oxidase- and NF-κB-Dependent Activation of Rac1.The American journal of pathology · 2015Article
- Inflammatory Cytokines Induce Expression of Chemokines by Human Retinal Cells: Role in Chemokine Receptor Mediated Age-related Macular Degeneration.Aging and disease · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo explore the molecular mechanisms by which the C-C chemokine receptor type 3 (CCR3) and chemokine (C-C motif) ligand 11 (CCL11) regulate choroidal endothelial cell (CEC) migration and the interactions with the vascular endothelial growth factor (VEGF) signaling pathway.
methodsHuman retinal sections from young and aged donor normal eyes were immunolabeled. By real-time PCR, CCR3 mRNA was measured in retinal pigmented epithelium (RPE)/choroids obtained from young and aged human donor eyes and in cultured CECs exposed to hydrogen peroxide. CCR3 ligand and CCL11- or VEGF-stimulated CEC migration was also measured in the presence of the CCR3 inhibitor or control using fluorescence microscopy. Activation of Rac1, phosphorylated Akt as a readout for phosphoinositol 3-kinase signaling, and VEGFR2 activation were measured in CECs incubated with CCL11, VEGF, or combined CCL11/VEGF.
resultsCCR3 was expressed to a greater level in older compared with that in younger human retinas or RPE/choroids. Ligand-activated CCR3 increased CEC migration, which was inhibited by the CCR3 inhibitor. Rac1 activity, p-Akt, and p-VEGFR2 were significantly increased in CECs incubated with CCL11. The CCR3 inhibitor prevented VEGF-induced CEC migration and Rac1 activation in CECs. Rac1 activity was additively increased in CECs treated with CCL11 and VEGF compared with that in cells with CCL11 or VEGF treatment alone. Ligand-activated CCR3 caused VEGFR2 phosphorylation and coimmunoprecipitation of VEGFR2 and CCR3.
conclusionsActivated CCR3 promotes CEC migration and Rac1 activation and causes an association with and activation of VEGFR2. Cross-talk between CCR3 and VEGF signaling exists and may be important in choroidal neovascularization in human age-related macular degeneration.
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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.