CoChat
Sign Up
Cited by 41Retinal Diseases and TreatmentsOcular Diseases and Behçet’s SyndromeAngiogenesis and VEGF in Cancer

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Suppression and Regression of Choroidal Neovascularization in Mice by a Novel CCR2 Antagonist, INCB3344

Open access
Xie, Ping, Kamei, Motohiro, Suzuki, Mihoko, Matsumura, Nagakazu, Nishida, Kentaro, Sakimoto, Susumu, Sakaguchi, Hirokazu, Nishida, Kohji·2011·PLoS ONE
DOI 10.1371/journal.pone.0028933PMC PMC3242774
Open this paper in CoChat — free accountOpen PDF

Abstract

PURPOSE: To investigate the effect of an intravitreally administered CCR2 antagonist, INCB3344, on a mouse model of choroidal neovascularization (CNV). METHODS: CNV was induced by laser photocoagulation on Day 0 in wild type mice. INCB3344 or vehicle was administered intravitreally immediately after laser application. On Day 14, CNV areas were measured on retinal pigment epithelium (RPE)-choroid flat mounts and histopathologic examination was performed on 7 µm-thick sections. Macrophage infiltration was evaluated by immunohistochemistry on RPE-choroid flat mounts and quantified by flow cytometry on Day 3. Expression of vascular endothelial growth factor (VEGF) protein in RPE-choroid tissue was examined by immunohistochemistry and ELISA, VEGF mRNA in sorted macrophages in RPE-choroid tissue was examine by real-time PCR and expression of phosphorylated extracellular signal-regulated kinase (p-ERK 1/2) in RPE-choroid tissue was measured by Western blot analysis on Day 3. We also evaluated the efficacy of intravitreal INCB3344 to spontaneous CNV detected in Cu, Zn-superoxide dismutase (SOD1) deficient mice. Changes in CNV size were assessed between pre- and 1week post-INCB3344 or vehicle administration in fundus photography and fluorescence angiography (FA). RESULTS: The mean CNV area in INCB3344-treated mice decreased by 42.4% compared with the vehicle-treated control mice (p<0.001). INCB3344 treatment significantly inhibited macrophage infiltration into the laser-irradiated area (p<0.001), and suppressed the expression of VEGF protein (p = 0.012), VEGF mRNA in infiltrating macrophages (p<0.001) and the phosphorylation of ERK1/2 (p<0.001). The area of spontaneous CNV in Sod1⁻/⁻ mice regressed by 70.35% in INCB3344-treated animals while no change was detected in vehicle-treated control mice (p<0.001). CONCLUSIONS: INCB3344 both inhibits newly forming CNV and regresses established CNV. Controlling inflammation by suppressing macrophage infiltration and angiogenic ability via the CCR-2/MCP-1 signal may be a useful therapeutic strategy for treating CNV associated with age-related macular degeneration.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0028933

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The MAPK signaling pathway plays a crucial role in the pathogenesis and progression of AMD.

    “Emerging evidence suggests that the MAPK signaling pathway plays a crucial role in the pathogenesis and progression of AMD 34-36 .”

    From rAAV-mediated Multi-miRNA Delivery Targeting MAPK Pathway Suppresses Laser-induced Choroidal Neovascularization in Mice (2026) · cites this paper as [34]

    The Results report MAPK-associated ERK1/2 activation in a mouse model of laser-induced choroidal neovascularization, and the Discussion links ERK1/2 to macrophage infiltration and VEGF production. The Introduction identifies neovascularization as a hallmark of wet AMD, but the paper does not establish that MAPK plays a crucial role in the pathogenesis and progression of AMD broadly. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 47

  1. SL Fine, 2000, Age-related macular degeneration., N Engl J Med, 342, 483, 10.1056/NEJM200002173420707 · DOI
  2. K Yamada, 2007, Inhibition of laser-induced choroidal neovascularization by atorvastatin by downregulation of monocyte chemotactic protein-1 synthesis in mice., Invest Ophthalmol Vis Sci, 48, 1839, 10.1167/iovs.06-1085 · DOI
  3. HE Grossniklaus, 2004, Choroidal neovascularization., Am J Ophthalmol, 137, 496, 10.1016/j.ajo.2003.09.042 · DOI · Paper page
  4. C Tsutsumi-Miyahara, 2004, The relative contributions of each subset of ocular infiltrated cells in experimental choroidal neovascularisation., Br J Ophthalmol, 88, 1217, 10.1136/bjo.2003.036392 · DOI
  5. HE Grossniklaus, 2002, Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization., Mol Vis, 8, 119
  6. M Kamei, 2007, Scavenger receptors for oxidized lipoprotein in age-related macular degeneration., Invest Ophthalmol Vis Sci, 48, 1801, 10.1167/iovs.06-0699 · DOI
  7. N Ferrara, 1997, The biology of vascular endothelial growth factor., Endocr Rev, 18, 4, 10.1210/edrv.18.1.0287 · DOI
  8. M Xiong, 1998, Production of vascular endothelial growth factor by murine macrophages: regulation by hypoxia, lactate, and the inducible nitric oxide synthase pathway., Am J Pathol, 153, 587, 10.1016/S0002-9440(10)65601-5 · DOI
  9. X Yi, 1997, Vascular endothelial growth factor expression in choroidal neovascularization in rats., Graefes Arch Clin Exp Ophthalmol, 235, 313, 10.1007/BF01739641 · DOI
  10. T Ishibashi, 1997, Expression of vascular endothelial growth factor in experimental choroidal neovascularization., Graefes Arch Clin Exp Ophthalmol, 235, 159, 10.1007/BF00941723 · DOI
  11. DG Espinosa-Heidmann, 2003, Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization., Invest Ophthalmol Vis Sci, 44, 3586, 10.1167/iovs.03-0038 · DOI
  12. E Sakurai, 2003, Macrophage depletion inhibits experimental choroidal neovascularization., Invest Ophthalmol Vis Sci, 44, 3578, 10.1167/iovs.03-0097 · DOI
  13. MB Furie, 1995, Chemokines and tissue injury., Am J Pathol, 146, 1287
  14. RM Strieter, 1996, “The good, the bad, and the ugly.” The role of chemokines in models of human disease., J Immunol, 156, 3583, 10.4049/jimmunol.156.10.3583 · DOI
  15. CA Power, 2001, The chemokine system: novel broad-spectrum therapeutic targets., Curr Opin Pharmacol, 1, 417, 10.1016/S1471-4892(01)00072-8 · DOI
  16. O Benny, 2010, Broad Spectrum Antiangiogenic Treatment for Ocular Neovascular Diseases., PLoS One, 5, e12515, 10.1371/journal.pone.0012515 · DOI
  17. K Noda, 2008, Vascular adhesion protein-1 blockade suppresses choroidal neovascularization., FASEB J, 22, 2928, 10.1096/fj.07-105346 · DOI
  18. S Satofuka, 2008, (Pro)renin receptor promotes choroidal neovascularization by activating its signal transduction and tissue renin-angiotensin system., Am J Pathol, 173, 1911, 10.2353/ajpath.2008.080457 · DOI
  19. RH Guymer, 2011, Identification of urinary biomarkers for age-related macular degeneration., Invest Ophthalmol Vis Sci, 52, 4639, 10.1167/iovs.10-7120 · DOI
  20. JB Jonas, 2010, Monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in exudative age-related macular degeneration., Arch Ophthalmol, 128, 1281, 10.1001/archophthalmol.2010.227 · DOI
  21. WA Kuziel, 1997, Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2., Proc Natl Acad Sci U S A, 94, 12053, 10.1073/pnas.94.22.12053 · DOI
  22. T Kurihara, 1997, Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor., J Exp Med, 186, 1757, 10.1084/jem.186.10.1757 · DOI
  23. B Lu, 1998, Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein-1-deficient mice., J Exp Med, 187, 601, 10.1084/jem.187.4.601 · DOI
  24. CM Brodmerkel, 2005, Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344., J Immunol, 175, 5370, 10.4049/jimmunol.175.8.5370 · DOI
  25. N Shin, 2009, Pharmacological characterization of INCB3344, a small molecule antagonist of human CCR2., Biochem Biophys Res Commun, 387, 251, 10.1016/j.bbrc.2009.06.135 · DOI
  26. MA Dansereau, 2008, Spinal CCL2 pronociceptive action is no longer effective in CCR2 receptor antagonist-treated rats., J Neurochem, 106, 757, 10.1111/j.1471-4159.2008.05429.x · DOI
  27. UF Luhmann, 2009, The drusenlike phenotype in aging Ccl2-knockout mice is caused by an accelerated accumulation of swollen autofluorescent subretinal macrophages., Invest Ophthalmol Vis Sci, 50, 5934, 10.1167/iovs.09-3462 · DOI
  28. C Campa, 2008, Effects of an anti-VEGF-A monoclonal antibody on laser-induced choroidal neovascularization in mice: optimizing methods to quantify vascular changes., Invest Ophthalmol Vis Sci, 49, 1178, 10.1167/iovs.07-1194 · DOI
  29. Y Imamura, 2006, Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: a model of age-related macular degeneration., Proc Natl Acad Sci U S A, 103, 11282, 10.1073/pnas.0602131103 · DOI · Paper page
  30. M Itaya, 2007, Upregulation of VEGF in murine retina via monocyte recruitment after retinal scatter laser photocoagulation., Invest Ophthalmol Vis Sci, 48, 5677, 10.1167/iovs.07-0156 · DOI
  31. JM Curry, 2008, M-CSF signals through the MAPK/ERK pathway via Sp1 to induce VEGF production and induces angiogenesis in vivo., PLoS One, 3, e3405, 10.1371/journal.pone.0003405 · DOI
  32. T Koto, 2007, Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice., Invest Ophthalmol Vis Sci, 48, 4328, 10.1167/iovs.06-1148 · DOI
  33. A Caicedo, 2005, Blood-derived macrophages infiltrate the retina and activate Muller glial cells under experimental choroidal neovascularization., Exp Eye Res, 81, 38, 10.1016/j.exer.2005.01.013 · DOI
  34. K Izumi-Nagai, 2007, Macular pigment lutein is antiinflammatory in preventing choroidal neovascularization., Arterioscler Thromb Vasc Biol, 27, 2555, 10.1161/ATVBAHA.107.151431 · DOI
  35. S Goyal, 2009, Amelioration of murine dry eye disease by topical antagonist to chemokine receptor 2., Arch Ophthalmol, 127, 882, 10.1001/archophthalmol.2009.125 · DOI
  36. MG Krzystolik, 2002, Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment., Arch Ophthalmol, 120, 338, 10.1001/archopht.120.3.338 · DOI
  37. A Kvanta, 1996, Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor., Invest Ophthalmol Vis Sci, 37, 1929
  38. J Wang, 2009, Amyloid-beta up-regulates complement factor B in retinal pigment epithelial cells through cytokines released from recruited macrophages/microglia: Another mechanism of complement activation in age-related macular degeneration., J Cell Physiol, 220, 119, 10.1002/jcp.21742 · DOI
  39. SW Cousins, 2004, Monocyte activation in patients with age-related macular degeneration: a biomarker of risk for choroidal neovascularization?, Arch Ophthalmol, 122, 1013, 10.1001/archopht.122.7.1013 · DOI
  40. H Oh, 1999, The potential angiogenic role of macrophages in the formation of choroidal neovascular membranes., Invest Ophthalmol Vis Sci, 40, 1891
  41. Y Inoue, 2007, Expression of hypoxia-inducible factor 1alpha and 2alpha in choroidal neovascular membranes associated with age-related macular degeneration., Br J Ophthalmol, 91, 1720, 10.1136/bjo.2006.111583 · DOI
  42. A Sodhi, 2002, Monocyte chemoattractant protein-1-induced activation of p42/44 MAPK and c-Jun in murine peritoneal macrophages: a potential pathway for macrophage activation., J Interferon Cytokine Res, 22, 517, 10.1089/10799900252981990 · DOI
  43. JH Wain, 2002, Leucocyte chemotaxis: Examination of mitogen-activated protein kinase and phosphoinositide 3-kinase activation by Monocyte Chemoattractant Proteins-1, -2, -3 and -4., Clin Exp Immunol, 127, 436, 10.1046/j.1365-2249.2002.01764.x · DOI
  44. H Yen, 1997, MCP-1-mediated chemotaxis requires activation of non-overlapping signal transduction pathways., J Leukoc Biol, 61, 529, 10.1002/jlb.61.4.529 · DOI
  45. B Cambien, 2001, Signal transduction involved in MCP-1-mediated monocytic transendothelial migration., Blood, 97, 359, 10.1182/blood.V97.2.359 · DOI
  46. S Liu, 2010, NDRG2 induced by oxidized LDL in macrophages antagonizes growth factor productions via selectively inhibiting ERK activation., Biochim Biophys Acta, 1801, 106, 10.1016/j.bbalip.2009.09.022 · DOI
  47. K Hashizume, 2008, Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice., Am J Pathol, 172, 1325, 10.2353/ajpath.2008.070730 · DOI

Cited by

Sorted by citations

Metadata

Authors
Xie, P., Kamei, M., Suzuki, M., Matsumura, N., Nishida, K., Sakimoto, S., Sakaguchi, H., & Nishida, K.
Affiliations
The University of Osaka (JP)
Corresponding author
Kamei, Motohiro
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2011-12-19
Volume
6
Issue
12
Pages
e28933
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0028933
PMC
PMC3242774
OpenAlex
W2035424618
Cited by
41
References
3
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 4 · 2015: 5 · 2014: 7 · 2013: 6 · 2012: 2
FWCI
4.50
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Japan Society for the Promotion of Science (21592231, 15591853)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
choroidal neovascularization, CCR2 antagonist, macrophage infiltration, vascular endothelial growth factor, ERK1/2 phosphorylation, laser-induced CNV, intravitreal administration, inflammation, choroid, retinal pigment epithelium, angiogenesis inhibition, mouse model
MeSH terms
Animals, Gene Expression Regulation, Lasers, Macrophages, Male, Mice, Inbred C57BL, Phosphorylation, Pyrrolidines, Mitogen-Activated Protein Kinase 1, Choroidal Neovascularization, Vascular Endothelial Growth Factor A, Mitogen-Activated Protein Kinase 3, Mice, Receptors, CCR2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review