IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38563-w.html
   My bibliography  Save this article

Antibody blockade of Jagged1 attenuates choroidal neovascularization

Author

Listed:
  • Torleif Tollefsrud Gjølberg

    (Oslo University Hospital Rikshospitalet
    University of Oslo and Oslo University Hospital
    Oslo University Hospital and University of Oslo)

  • Jonas Aakre Wik

    (Oslo University Hospital Rikshospitalet
    University of Oslo)

  • Hanna Johannessen

    (Oslo University Hospital Rikshospitalet
    Oslo University Hospital Rikshospitalet)

  • Stig Krüger

    (Oslo University Hospital Rikshospitalet)

  • Nicola Bassi

    (Oslo University Hospital Rikshospitalet)

  • Panagiotis F. Christopoulos

    (Oslo University Hospital Rikshospitalet)

  • Malin Bern

    (Oslo University Hospital Rikshospitalet
    University of Oslo and Oslo University Hospital)

  • Stian Foss

    (Oslo University Hospital Rikshospitalet
    University of Oslo and Oslo University Hospital)

  • Goran Petrovski

    (Oslo University Hospital and University of Oslo)

  • Morten C. Moe

    (Oslo University Hospital and University of Oslo)

  • Guttorm Haraldsen

    (Oslo University Hospital Rikshospitalet)

  • Johanna Hol Fosse

    (Oslo University Hospital Rikshospitalet)

  • Bjørn Steen Skålhegg

    (University of Oslo)

  • Jan Terje Andersen

    (Oslo University Hospital Rikshospitalet
    University of Oslo and Oslo University Hospital)

  • Eirik Sundlisæter

    (Oslo University Hospital Rikshospitalet)

Abstract

Antibody-based blocking of vascular endothelial growth factor (VEGF) reduces choroidal neovascularization (CNV) and retinal edema, rescuing vision in patients with neovascular age-related macular degeneration (nAMD). However, poor response and resistance to anti-VEGF treatment occurs. We report that targeting the Notch ligand Jagged1 by a monoclonal antibody reduces neovascular lesion size, number of activated phagocytes and inflammatory markers and vascular leakage in an experimental CNV mouse model. Additionally, we demonstrate that Jagged1 is expressed in mouse and human eyes, and that Jagged1 expression is independent of VEGF signaling in human endothelial cells. When anti-Jagged1 was combined with anti-VEGF in mice, the decrease in lesion size exceeded that of either antibody alone. The therapeutic effect was solely dependent on blocking, as engineering antibodies to abolish effector functions did not impair the therapeutic effect. Targeting of Jagged1 alone or in combination with anti-VEGF may thus be an attractive strategy to attenuate CNV-bearing diseases.

Suggested Citation

  • Torleif Tollefsrud Gjølberg & Jonas Aakre Wik & Hanna Johannessen & Stig Krüger & Nicola Bassi & Panagiotis F. Christopoulos & Malin Bern & Stian Foss & Goran Petrovski & Morten C. Moe & Guttorm Haral, 2023. "Antibody blockade of Jagged1 attenuates choroidal neovascularization," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38563-w
    DOI: 10.1038/s41467-023-38563-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38563-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-38563-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Algirdas Grevys & Jeannette Nilsen & Kine M. K. Sand & Muluneh B. Daba & Inger Øynebråten & Malin Bern & Martin B. McAdam & Stian Foss & Tilman Schlothauer & Terje E. Michaelsen & Gregory J. Christian, 2018. "A human endothelial cell-based recycling assay for screening of FcRn targeted molecules," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    2. Daniel Lafkas & Amy Shelton & Cecilia Chiu & Gladys de Leon Boenig & Yongmei Chen & Scott S. Stawicki & Christian Siltanen & Mike Reichelt & Meijuan Zhou & Xiumin Wu & Jeffrey Eastham-Anderson & Heath, 2015. "Therapeutic antibodies reveal Notch control of transdifferentiation in the adult lung," Nature, Nature, vol. 528(7580), pages 127-131, December.
    3. William J. Polacheck & Matthew L. Kutys & Jinling Yang & Jeroen Eyckmans & Yinyu Wu & Hema Vasavada & Karen K. Hirschi & Christopher S. Chen, 2017. "A non-canonical Notch complex regulates adherens junctions and vascular barrier function," Nature, Nature, vol. 552(7684), pages 258-262, December.
    4. Joy G. Ghosh & Andrew A. Nguyen & Chad E. Bigelow & Stephen Poor & Yubin Qiu & Nalini Rangaswamy & Richard Ornberg & Brittany Jackson & Howard Mak & Tucker Ezell & Vania Kenanova & Elisa de la Cruz & , 2017. "Long-acting protein drugs for the treatment of ocular diseases," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Stian Foss & Siri A. Sakya & Leire Aguinagalde & Marta Lustig & Jutamas Shaughnessy & Ana Rita Cruz & Lisette Scheepmaker & Line Mathiesen & Fulgencio Ruso-Julve & Aina Karen Anthi & Torleif Tollefsru, 2024. "Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Maximilian Brinkhaus & Erwin Pannecoucke & Elvera J. Kooi & Arthur E. H. Bentlage & Ninotska I. L. Derksen & Julie Andries & Bianca Balbino & Magdalena Sips & Peter Ulrichts & Peter Verheesen & Hans H, 2022. "The Fab region of IgG impairs the internalization pathway of FcRn upon Fc engagement," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Songbai Zhang & Ayako Miyakawa & Malin Wickström & Cecilia Dyberg & Lauri Louhivuori & Manuel Varas-Godoy & Kati Kemppainen & Shigeaki Kanatani & Dagmara Kaczynska & Ivar Dehnisch Ellström & Lotta Elf, 2022. "GIT1 protects against breast cancer growth through negative regulation of Notch," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Mayra Cruz Tleugabulova & Sandra P. Melo & Aaron Wong & Alexander Arlantico & Meizi Liu & Joshua D. Webster & Julia Lau & Antonie Lechner & Basak Corak & Jonathan J. Hodgins & Venkata S. Garlapati & M, 2024. "Induction of a distinct macrophage population and protection from lung injury and fibrosis by Notch2 blockade," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Douglas G. Brownfield & Alex Diaz Arce & Elisa Ghelfi & Astrid Gillich & Tushar J. Desai & Mark A. Krasnow, 2022. "Alveolar cell fate selection and lifelong maintenance of AT2 cells by FGF signaling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38563-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.