Antibody blockade of Jagged1 attenuates choroidal neovascularization

Nat Commun. 2023 May 30;14(1):3109. doi: 10.1038/s41467-023-38563-w.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antibodies, Blocking / therapeutic use
  • Choroidal Neovascularization* / pathology
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Humans
  • Mice
  • Signal Transduction / physiology
  • Vascular Endothelial Growth Factor A* / metabolism


  • Vascular Endothelial Growth Factor A
  • Antibodies, Blocking
  • Angiogenesis Inhibitors