Antibody blockade of Jagged1 attenuates choroidal neovascularization
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 re...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38563-w |
| _version_ | 1797811413609086976 |
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| author | 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 Haraldsen Johanna Hol Fosse Bjørn Steen Skålhegg Jan Terje Andersen Eirik Sundlisæter |
| author_facet | 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 Haraldsen Johanna Hol Fosse Bjørn Steen Skålhegg Jan Terje Andersen Eirik Sundlisæter |
| author_sort | Torleif Tollefsrud Gjølberg |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T07:22:19Z |
| format | Article |
| id | doaj.art-76fcbbf1b309412aacb2029fbbf2cf3a |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T07:22:19Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-76fcbbf1b309412aacb2029fbbf2cf3a2023-06-04T11:33:11ZengNature PortfolioNature Communications2041-17232023-05-0114111910.1038/s41467-023-38563-wAntibody blockade of Jagged1 attenuates choroidal neovascularizationTorleif Tollefsrud Gjølberg0Jonas Aakre Wik1Hanna Johannessen2Stig Krüger3Nicola Bassi4Panagiotis F. Christopoulos5Malin Bern6Stian Foss7Goran Petrovski8Morten C. Moe9Guttorm Haraldsen10Johanna Hol Fosse11Bjørn Steen Skålhegg12Jan Terje Andersen13Eirik Sundlisæter14Department of Immunology, Oslo University Hospital RikshospitaletDepartment of Pathology, Oslo University Hospital RikshospitaletDepartment of Pathology, Oslo University Hospital RikshospitaletDepartment of Pathology, Oslo University Hospital RikshospitaletDepartment of Pathology, Oslo University Hospital RikshospitaletDepartment of Pathology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Immunology, Oslo University Hospital RikshospitaletCenter of Eye Research, Department of Ophthalmology, Oslo University Hospital and University of OsloCenter of Eye Research, Department of Ophthalmology, Oslo University Hospital and University of OsloDepartment of Pathology, Oslo University Hospital RikshospitaletDepartment of Pathology, Oslo University Hospital RikshospitaletDepartment of Nutrition, Division of Molecular Nutrition, Institute of Basic Medical Sciences, University of OsloDepartment of Immunology, Oslo University Hospital RikshospitaletDepartment of Pathology, Oslo University Hospital RikshospitaletAbstract 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.https://doi.org/10.1038/s41467-023-38563-w |
| spellingShingle | 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 Haraldsen Johanna Hol Fosse Bjørn Steen Skålhegg Jan Terje Andersen Eirik Sundlisæter Antibody blockade of Jagged1 attenuates choroidal neovascularization Nature Communications |
| title | Antibody blockade of Jagged1 attenuates choroidal neovascularization |
| title_full | Antibody blockade of Jagged1 attenuates choroidal neovascularization |
| title_fullStr | Antibody blockade of Jagged1 attenuates choroidal neovascularization |
| title_full_unstemmed | Antibody blockade of Jagged1 attenuates choroidal neovascularization |
| title_short | Antibody blockade of Jagged1 attenuates choroidal neovascularization |
| title_sort | antibody blockade of jagged1 attenuates choroidal neovascularization |
| url | https://doi.org/10.1038/s41467-023-38563-w |
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