Co-inhibition of PGF and VEGF blocks their expression in mononuclear phagocytes and limits neovascularization and leakage in the murine retina View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Carsten Balser, Anne Wolf, Marc Herb, Thomas Langmann

ABSTRACT

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly. The neovascular (wet) form of AMD can be treated with intravitreal injections of different anti-vascular endothelial growth factor (VEGF) agents. Placental growth factor (PGF) is another member of the VEGF family of cytokines with pro-angiogenic and pro-inflammatory effects. Here, we aimed to compare single and combined inhibition of VEGF-A and PGF in the laser-induced mouse model of choroidal neovascularization (CNV) with a focus on the effects on retinal mononuclear phagocytes. METHODS: CNV was induced in C57BL/6J mice using a YAG-Laser. Immediately after laser damage antibodies against VEGF-A (aVEGF), anti-PGF (aPGF), aVEGF combined with aPGF, aflibercept, or IgG control were injected intravitreally in both eyes. Three and 7 days after laser damage, the vascular leakage was determined by fluorescence angiography. Lectin staining of retinal and RPE/choroidal flat mounts was used to monitor CNV. In situ mRNA co-expression of Iba1, VEGF and PGF were quantified using in situ hybridization. Retinal and RPE/choroidal protein levels of VEGF and PGF as well as the pro-inflammatory cytokines IL-6, IL1-beta, and TNF were determined by ELISA. RESULTS: Early (day 3) and intermediate (day 7) vascular leakage and CNV were significantly inhibited by PGF and VEGF-A co-inhibition, most effectively with the trap molecule aflibercept. While VEGF-A blockage alone had no effects, trapping PGF especially with aflibercept prevented the accumulation of reactive microglia and macrophages in laser lesions. The lesion-related mRNA expression and secretion of VEGF-A and PGF by mononuclear phagocytes were potently suppressed by PGF and partially by VEGF-A inhibition. Protein levels of IL-6 and IL1-beta were strongly reduced in all treatment groups. CONCLUSIONS: Retinal inhibition of PGF in combination with VEGF-A prevents vascular leakage and CNV possibly via modulating their own expression in mononuclear phagocytes. PGF-related, optimized strategies to target inflammation-mediated angiogenesis may help to increase efficacy and reduce non-responders in the treatment of wet AMD patients. More... »

PAGES

26

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12974-019-1419-2

DOI

http://dx.doi.org/10.1186/s12974-019-1419-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111989424

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30732627


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1113", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Ophthalmology and Optometry", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "University of Cologne", 
          "id": "https://www.grid.ac/institutes/grid.6190.e", 
          "name": [
            "Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, 50931, Cologne, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Balser", 
        "givenName": "Carsten", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Cologne", 
          "id": "https://www.grid.ac/institutes/grid.6190.e", 
          "name": [
            "Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, 50931, Cologne, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wolf", 
        "givenName": "Anne", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Institute for Medical Microbiology, Immunology and Hygiene, 50931, Cologne, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Herb", 
        "givenName": "Marc", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Cologne", 
          "id": "https://www.grid.ac/institutes/grid.6190.e", 
          "name": [
            "Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, 50931, Cologne, Germany", 
            "Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Langmann", 
        "givenName": "Thomas", 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1016/j.cell.2010.02.039", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000094705"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jcp.10246", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001330054"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/aos.12251", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001520954"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1167/iovs.12-10655", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004477116"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1159/000373990", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005491187"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1167/iovs.15-16748", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011335592"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.preteyeres.2014.11.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015474700"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1523/jneurosci.2468-15.2015", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017569264"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1167/iovs.03-0038", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017996746"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1167/iovs.03-0097", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020576769"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.exer.2014.02.024", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023643382"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00125-006-0539-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026602856", 
          "https://doi.org/10.1007/s00125-006-0539-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00125-006-0539-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026602856", 
          "https://doi.org/10.1007/s00125-006-0539-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1167/iovs.02-1092", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026686745"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1523/jneurosci.3575-15.2016", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027980789"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1167/iovs.15-16793", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028935783"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1182/blood-2002-11-3422", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028957226"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1042/bsr20110077", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028963493"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1167/iovs.12-10658", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029467167"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1189/jlb.3ri0615-239r", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031299222"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/jcmm.12151", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031787424"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10456-016-9515-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032405000", 
          "https://doi.org/10.1007/s10456-016-9515-8"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10456-016-9515-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032405000", 
          "https://doi.org/10.1007/s10456-016-9515-8"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1167/iovs.15-16898", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032413742"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bbi.2014.11.009", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043184400"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1159/000119877", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043585164"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jcp.22708", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047319209"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s2214-109x(13)70145-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048289897"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2147/dddt.s115121", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049776102"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s12915-014-0055-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051464058", 
          "https://doi.org/10.1186/s12915-014-0055-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s12915-014-0055-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051464058", 
          "https://doi.org/10.1186/s12915-014-0055-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1075055333", 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nprot.2017.032", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085126522", 
          "https://doi.org/10.1038/nprot.2017.032"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.preteyeres.2017.06.002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085915911"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.exer.2017.09.012", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1091977949"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1167/iovs.16-21283", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1092085832"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1167/iovs.17-22471", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1092480307"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s12886-018-0785-3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1104289161", 
          "https://doi.org/10.1186/s12886-018-0785-3"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1159/000490430", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1105550357"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1159/000490430", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1105550357"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.jphs.2018.07.010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1106004345"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2147/opth.s171636", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107228320"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.preteyeres.2018.10.006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107908425"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.preteyeres.2018.10.006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107908425"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.preteyeres.2018.10.006", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107908425"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2019-12", 
    "datePublishedReg": "2019-12-01", 
    "description": "BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly. The neovascular (wet) form of AMD can be treated with intravitreal injections of different anti-vascular endothelial growth factor (VEGF) agents. Placental growth factor (PGF) is another member of the VEGF family of cytokines with pro-angiogenic and pro-inflammatory effects. Here, we aimed to compare single and combined inhibition of VEGF-A and PGF in the laser-induced mouse model of choroidal neovascularization (CNV) with a focus on the effects on retinal mononuclear phagocytes.\nMETHODS: CNV was induced in C57BL/6J mice using a YAG-Laser. Immediately after laser damage antibodies against VEGF-A (aVEGF), anti-PGF (aPGF), aVEGF combined with aPGF, aflibercept, or IgG control were injected intravitreally in both eyes. Three and 7\u00a0days after laser damage, the vascular leakage was determined by fluorescence angiography. Lectin staining of retinal and RPE/choroidal flat mounts was used to monitor CNV. In situ mRNA co-expression of Iba1, VEGF and PGF were quantified using in situ hybridization. Retinal and RPE/choroidal protein levels of VEGF and PGF as well as the pro-inflammatory cytokines IL-6, IL1-beta, and TNF were determined by ELISA.\nRESULTS: Early (day 3) and intermediate (day 7) vascular leakage and CNV were significantly inhibited by PGF and VEGF-A co-inhibition, most effectively with the trap molecule aflibercept. While VEGF-A blockage alone had no effects, trapping PGF especially with aflibercept prevented the accumulation of reactive microglia and macrophages in laser lesions. The lesion-related mRNA expression and secretion of VEGF-A and PGF by mononuclear phagocytes were potently suppressed by PGF and partially by VEGF-A inhibition. Protein levels of IL-6 and IL1-beta were strongly reduced in all treatment groups.\nCONCLUSIONS: Retinal inhibition of PGF in combination with VEGF-A prevents vascular leakage and CNV possibly via modulating their own expression in mononuclear phagocytes. PGF-related, optimized strategies to target inflammation-mediated angiogenesis may help to increase efficacy and reduce non-responders in the treatment of wet AMD patients.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1186/s12974-019-1419-2", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1034001", 
        "issn": [
          "1742-2094"
        ], 
        "name": "Journal of Neuroinflammation", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "16"
      }
    ], 
    "name": "Co-inhibition of PGF and VEGF blocks their expression in mononuclear phagocytes and limits neovascularization and leakage in the murine retina", 
    "pagination": "26", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "7ec82075fbe1dd004b1fda49c56a29041978a6bc346807beab42286d3de1a954"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "30732627"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101222974"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/s12974-019-1419-2"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1111989424"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/s12974-019-1419-2", 
      "https://app.dimensions.ai/details/publication/pub.1111989424"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T09:14", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000338_0000000338/records_47997_00000002.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://link.springer.com/10.1186%2Fs12974-019-1419-2"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s12974-019-1419-2'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12974-019-1419-2'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12974-019-1419-2'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s12974-019-1419-2'


 

This table displays all metadata directly associated to this object as RDF triples.

209 TRIPLES      21 PREDICATES      68 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/s12974-019-1419-2 schema:about anzsrc-for:11
2 anzsrc-for:1113
3 schema:author N71dd709ccdbc4544a239ea197cc8372a
4 schema:citation sg:pub.10.1007/s00125-006-0539-2
5 sg:pub.10.1007/s10456-016-9515-8
6 sg:pub.10.1038/nprot.2017.032
7 sg:pub.10.1186/s12886-018-0785-3
8 sg:pub.10.1186/s12915-014-0055-7
9 https://app.dimensions.ai/details/publication/pub.1075055333
10 https://doi.org/10.1002/jcp.10246
11 https://doi.org/10.1002/jcp.22708
12 https://doi.org/10.1016/j.bbi.2014.11.009
13 https://doi.org/10.1016/j.cell.2010.02.039
14 https://doi.org/10.1016/j.exer.2014.02.024
15 https://doi.org/10.1016/j.exer.2017.09.012
16 https://doi.org/10.1016/j.jphs.2018.07.010
17 https://doi.org/10.1016/j.preteyeres.2014.11.004
18 https://doi.org/10.1016/j.preteyeres.2017.06.002
19 https://doi.org/10.1016/j.preteyeres.2018.10.006
20 https://doi.org/10.1016/s2214-109x(13)70145-1
21 https://doi.org/10.1042/bsr20110077
22 https://doi.org/10.1111/aos.12251
23 https://doi.org/10.1111/jcmm.12151
24 https://doi.org/10.1159/000119877
25 https://doi.org/10.1159/000373990
26 https://doi.org/10.1159/000490430
27 https://doi.org/10.1167/iovs.02-1092
28 https://doi.org/10.1167/iovs.03-0038
29 https://doi.org/10.1167/iovs.03-0097
30 https://doi.org/10.1167/iovs.12-10655
31 https://doi.org/10.1167/iovs.12-10658
32 https://doi.org/10.1167/iovs.15-16748
33 https://doi.org/10.1167/iovs.15-16793
34 https://doi.org/10.1167/iovs.15-16898
35 https://doi.org/10.1167/iovs.16-21283
36 https://doi.org/10.1167/iovs.17-22471
37 https://doi.org/10.1182/blood-2002-11-3422
38 https://doi.org/10.1189/jlb.3ri0615-239r
39 https://doi.org/10.1523/jneurosci.2468-15.2015
40 https://doi.org/10.1523/jneurosci.3575-15.2016
41 https://doi.org/10.2147/dddt.s115121
42 https://doi.org/10.2147/opth.s171636
43 schema:datePublished 2019-12
44 schema:datePublishedReg 2019-12-01
45 schema:description BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly. The neovascular (wet) form of AMD can be treated with intravitreal injections of different anti-vascular endothelial growth factor (VEGF) agents. Placental growth factor (PGF) is another member of the VEGF family of cytokines with pro-angiogenic and pro-inflammatory effects. Here, we aimed to compare single and combined inhibition of VEGF-A and PGF in the laser-induced mouse model of choroidal neovascularization (CNV) with a focus on the effects on retinal mononuclear phagocytes. METHODS: CNV was induced in C57BL/6J mice using a YAG-Laser. Immediately after laser damage antibodies against VEGF-A (aVEGF), anti-PGF (aPGF), aVEGF combined with aPGF, aflibercept, or IgG control were injected intravitreally in both eyes. Three and 7 days after laser damage, the vascular leakage was determined by fluorescence angiography. Lectin staining of retinal and RPE/choroidal flat mounts was used to monitor CNV. In situ mRNA co-expression of Iba1, VEGF and PGF were quantified using in situ hybridization. Retinal and RPE/choroidal protein levels of VEGF and PGF as well as the pro-inflammatory cytokines IL-6, IL1-beta, and TNF were determined by ELISA. RESULTS: Early (day 3) and intermediate (day 7) vascular leakage and CNV were significantly inhibited by PGF and VEGF-A co-inhibition, most effectively with the trap molecule aflibercept. While VEGF-A blockage alone had no effects, trapping PGF especially with aflibercept prevented the accumulation of reactive microglia and macrophages in laser lesions. The lesion-related mRNA expression and secretion of VEGF-A and PGF by mononuclear phagocytes were potently suppressed by PGF and partially by VEGF-A inhibition. Protein levels of IL-6 and IL1-beta were strongly reduced in all treatment groups. CONCLUSIONS: Retinal inhibition of PGF in combination with VEGF-A prevents vascular leakage and CNV possibly via modulating their own expression in mononuclear phagocytes. PGF-related, optimized strategies to target inflammation-mediated angiogenesis may help to increase efficacy and reduce non-responders in the treatment of wet AMD patients.
46 schema:genre research_article
47 schema:inLanguage en
48 schema:isAccessibleForFree true
49 schema:isPartOf N39afd694049141f7a4b3a3dee62c9e86
50 Ne4933366069a4b468727235a52605b40
51 sg:journal.1034001
52 schema:name Co-inhibition of PGF and VEGF blocks their expression in mononuclear phagocytes and limits neovascularization and leakage in the murine retina
53 schema:pagination 26
54 schema:productId N0250b6e98c0448f7ba615817accc62c0
55 N02c5717336e54a4f8e66dc8d6c7e5aad
56 N1f375b1786434ed3aac6f20c36604fe2
57 N68c5c12c0aaa404e844008039c8c88d7
58 Nc53e788b4f7b4a61a3939024a079f956
59 schema:sameAs https://app.dimensions.ai/details/publication/pub.1111989424
60 https://doi.org/10.1186/s12974-019-1419-2
61 schema:sdDatePublished 2019-04-11T09:14
62 schema:sdLicense https://scigraph.springernature.com/explorer/license/
63 schema:sdPublisher N5ec5cc9ebb77494ead143a16e9b678ed
64 schema:url https://link.springer.com/10.1186%2Fs12974-019-1419-2
65 sgo:license sg:explorer/license/
66 sgo:sdDataset articles
67 rdf:type schema:ScholarlyArticle
68 N0250b6e98c0448f7ba615817accc62c0 schema:name pubmed_id
69 schema:value 30732627
70 rdf:type schema:PropertyValue
71 N02c5717336e54a4f8e66dc8d6c7e5aad schema:name nlm_unique_id
72 schema:value 101222974
73 rdf:type schema:PropertyValue
74 N1f375b1786434ed3aac6f20c36604fe2 schema:name doi
75 schema:value 10.1186/s12974-019-1419-2
76 rdf:type schema:PropertyValue
77 N39afd694049141f7a4b3a3dee62c9e86 schema:issueNumber 1
78 rdf:type schema:PublicationIssue
79 N3c96b451f88e4b84b83a9ba022dea610 schema:affiliation https://www.grid.ac/institutes/grid.6190.e
80 schema:familyName Wolf
81 schema:givenName Anne
82 rdf:type schema:Person
83 N495dbcb9f25d495aa06643a25f1746a6 schema:affiliation https://www.grid.ac/institutes/grid.6190.e
84 schema:familyName Balser
85 schema:givenName Carsten
86 rdf:type schema:Person
87 N55c4dbba0f59439e93527de84bdb509b rdf:first N879c50a10aa7449e96bc6880a1a84fb5
88 rdf:rest rdf:nil
89 N5ec5cc9ebb77494ead143a16e9b678ed schema:name Springer Nature - SN SciGraph project
90 rdf:type schema:Organization
91 N639e69be927243659d9d96759c93f2a4 rdf:first N9b29324e314a4c15826135310abb82df
92 rdf:rest N55c4dbba0f59439e93527de84bdb509b
93 N68c5c12c0aaa404e844008039c8c88d7 schema:name readcube_id
94 schema:value 7ec82075fbe1dd004b1fda49c56a29041978a6bc346807beab42286d3de1a954
95 rdf:type schema:PropertyValue
96 N71dd709ccdbc4544a239ea197cc8372a rdf:first N495dbcb9f25d495aa06643a25f1746a6
97 rdf:rest Naba54fdf86024b208b292bf80a713ef6
98 N7b6bcce7ddae4636b3b40255c0a71966 schema:name Institute for Medical Microbiology, Immunology and Hygiene, 50931, Cologne, Germany
99 rdf:type schema:Organization
100 N879c50a10aa7449e96bc6880a1a84fb5 schema:affiliation https://www.grid.ac/institutes/grid.6190.e
101 schema:familyName Langmann
102 schema:givenName Thomas
103 rdf:type schema:Person
104 N9b29324e314a4c15826135310abb82df schema:affiliation N7b6bcce7ddae4636b3b40255c0a71966
105 schema:familyName Herb
106 schema:givenName Marc
107 rdf:type schema:Person
108 Naba54fdf86024b208b292bf80a713ef6 rdf:first N3c96b451f88e4b84b83a9ba022dea610
109 rdf:rest N639e69be927243659d9d96759c93f2a4
110 Nc53e788b4f7b4a61a3939024a079f956 schema:name dimensions_id
111 schema:value pub.1111989424
112 rdf:type schema:PropertyValue
113 Ne4933366069a4b468727235a52605b40 schema:volumeNumber 16
114 rdf:type schema:PublicationVolume
115 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
116 schema:name Medical and Health Sciences
117 rdf:type schema:DefinedTerm
118 anzsrc-for:1113 schema:inDefinedTermSet anzsrc-for:
119 schema:name Ophthalmology and Optometry
120 rdf:type schema:DefinedTerm
121 sg:journal.1034001 schema:issn 1742-2094
122 schema:name Journal of Neuroinflammation
123 rdf:type schema:Periodical
124 sg:pub.10.1007/s00125-006-0539-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026602856
125 https://doi.org/10.1007/s00125-006-0539-2
126 rdf:type schema:CreativeWork
127 sg:pub.10.1007/s10456-016-9515-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032405000
128 https://doi.org/10.1007/s10456-016-9515-8
129 rdf:type schema:CreativeWork
130 sg:pub.10.1038/nprot.2017.032 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085126522
131 https://doi.org/10.1038/nprot.2017.032
132 rdf:type schema:CreativeWork
133 sg:pub.10.1186/s12886-018-0785-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1104289161
134 https://doi.org/10.1186/s12886-018-0785-3
135 rdf:type schema:CreativeWork
136 sg:pub.10.1186/s12915-014-0055-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051464058
137 https://doi.org/10.1186/s12915-014-0055-7
138 rdf:type schema:CreativeWork
139 https://app.dimensions.ai/details/publication/pub.1075055333 schema:CreativeWork
140 https://doi.org/10.1002/jcp.10246 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001330054
141 rdf:type schema:CreativeWork
142 https://doi.org/10.1002/jcp.22708 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047319209
143 rdf:type schema:CreativeWork
144 https://doi.org/10.1016/j.bbi.2014.11.009 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043184400
145 rdf:type schema:CreativeWork
146 https://doi.org/10.1016/j.cell.2010.02.039 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000094705
147 rdf:type schema:CreativeWork
148 https://doi.org/10.1016/j.exer.2014.02.024 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023643382
149 rdf:type schema:CreativeWork
150 https://doi.org/10.1016/j.exer.2017.09.012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091977949
151 rdf:type schema:CreativeWork
152 https://doi.org/10.1016/j.jphs.2018.07.010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1106004345
153 rdf:type schema:CreativeWork
154 https://doi.org/10.1016/j.preteyeres.2014.11.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015474700
155 rdf:type schema:CreativeWork
156 https://doi.org/10.1016/j.preteyeres.2017.06.002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085915911
157 rdf:type schema:CreativeWork
158 https://doi.org/10.1016/j.preteyeres.2018.10.006 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107908425
159 rdf:type schema:CreativeWork
160 https://doi.org/10.1016/s2214-109x(13)70145-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048289897
161 rdf:type schema:CreativeWork
162 https://doi.org/10.1042/bsr20110077 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028963493
163 rdf:type schema:CreativeWork
164 https://doi.org/10.1111/aos.12251 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001520954
165 rdf:type schema:CreativeWork
166 https://doi.org/10.1111/jcmm.12151 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031787424
167 rdf:type schema:CreativeWork
168 https://doi.org/10.1159/000119877 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043585164
169 rdf:type schema:CreativeWork
170 https://doi.org/10.1159/000373990 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005491187
171 rdf:type schema:CreativeWork
172 https://doi.org/10.1159/000490430 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105550357
173 rdf:type schema:CreativeWork
174 https://doi.org/10.1167/iovs.02-1092 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026686745
175 rdf:type schema:CreativeWork
176 https://doi.org/10.1167/iovs.03-0038 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017996746
177 rdf:type schema:CreativeWork
178 https://doi.org/10.1167/iovs.03-0097 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020576769
179 rdf:type schema:CreativeWork
180 https://doi.org/10.1167/iovs.12-10655 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004477116
181 rdf:type schema:CreativeWork
182 https://doi.org/10.1167/iovs.12-10658 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029467167
183 rdf:type schema:CreativeWork
184 https://doi.org/10.1167/iovs.15-16748 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011335592
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1167/iovs.15-16793 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028935783
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1167/iovs.15-16898 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032413742
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1167/iovs.16-21283 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092085832
191 rdf:type schema:CreativeWork
192 https://doi.org/10.1167/iovs.17-22471 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092480307
193 rdf:type schema:CreativeWork
194 https://doi.org/10.1182/blood-2002-11-3422 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028957226
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1189/jlb.3ri0615-239r schema:sameAs https://app.dimensions.ai/details/publication/pub.1031299222
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1523/jneurosci.2468-15.2015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017569264
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1523/jneurosci.3575-15.2016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027980789
201 rdf:type schema:CreativeWork
202 https://doi.org/10.2147/dddt.s115121 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049776102
203 rdf:type schema:CreativeWork
204 https://doi.org/10.2147/opth.s171636 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107228320
205 rdf:type schema:CreativeWork
206 https://www.grid.ac/institutes/grid.6190.e schema:alternateName University of Cologne
207 schema:name Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931, Cologne, Germany
208 Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, 50931, Cologne, Germany
209 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...