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Myeloid-resident neuropilin-1 promotes choroidal neovascularization while mitigating inflammation
Elisabeth M M A Andriessen1, François Binet2,3, Frédérik Fournier4
1Department of Biomedical Sciences, University of Montreal, Montreal, QC, Canada.
EMBO Molecular Medicine
|April 20, 2021
Summary
Neuropilin-1 (NRP1) expressing myeloid cells drive choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Targeting NRP1 ligands offers a new therapeutic strategy for treating neovascular AMD.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Age-related macular degeneration (AMD) is a major cause of vision loss.
- Choroidal neovascularization (CNV) is a key pathological feature of wet AMD.
Purpose of the Study:
- To investigate the role of neuropilin-1 (NRP1) and its ligands in AMD-associated CNV.
- To explore NRP1-expressing myeloid cells as therapeutic targets for neovascular AMD.
Main Methods:
- Vitreous samples from AMD patients were analyzed for NRP1 ligand levels.
- The function of NRP1-expressing myeloid cells in CNV was assessed.
- The therapeutic efficacy of an NRP1-derived trap was evaluated in reducing CNV.
Main Results:
- Ligands for NRP1, including Semaphorin 3A and VEGF-A, were elevated in AMD patients with active CNV.
- NRP1-expressing myeloid cells were found to promote and sustain CNV.
- NRP1 expression on myeloid cells is crucial for regulating inflammatory factors like IL6 and IL1β.
- An NRP1-derived trap significantly reduced CNV in experimental models.
Conclusions:
- NRP1-expressing myeloid cells play a critical role in promoting pathological angiogenesis in CNV.
- Targeting NRP1 ligands with a novel trap represents a promising therapeutic approach for neovascular AMD.
