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Proangiogenic characteristics of activated macrophages from patients with age-related macular degeneration
Shira Hagbi-Levi1, Michelle Grunin1, Tareq Jaouni1
1Department of Ophthalmology, Hadassah-Hebrew University Medical Center and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
Abstract:
Macrophages were previously implicated in the pathogenesis of neovascular age-related macular degeneration (nvAMD). It is unclear if a specific macrophage phenotype is associated with nvAMD, and if macrophages from nvAMD patients are more pathogenic as compared with controls. To address these issues, we evaluated macrophages derived from peripheral blood monocytes of nvAMD patients and age-matched controls. Macrophages were assessed in terms of their expression profile and of their angiogenic potential in the choroid sprouting assay and the rat model of laser-induced choroidal neovascularization. Results showed a proangiogenic and inflammatory gene and protein expression profiles in classic (M[IFNγ and LPS]) and alternative (M[IL-4 and IL-13]) polarized macrophages. Furthermore, activated macrophages, particularly of the M(IFNγ and LPS) phenotype from nvAMD patients, were proangiogenic ex vivo and in vivo. These findings implicate activated human macrophages, particularly M(IFNγ and LPS) macrophages from nvAMD patients, in nvAMD. Further research is required to determine whether activated macrophages can serve as therapeutic targets in nvAMD.
Insights
Activated macrophages, especially M(IFNγ and LPS) types from patients with neovascular age-related macular degeneration (nvAMD), promote blood vessel growth. This suggests these specific macrophages could be therapeutic targets for treating nvAMD.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Macrophages are implicated in neovascular age-related macular degeneration (nvAMD) pathogenesis.
- The specific macrophage phenotype associated with nvAMD and their pathogenic potential remain unclear.
Purpose of the Study:
- To evaluate macrophages derived from peripheral blood monocytes of nvAMD patients and controls.
- To assess macrophage expression profiles and angiogenic potential.
Main Methods:
- Polarization of macrophages into classic (M[IFNγ and LPS]) and alternative (M[IL-4 and IL-13]) phenotypes.
- Assessment of gene and protein expression profiles.
- Evaluation of angiogenic potential using choroid sprouting assay and a rat model of laser-induced choroidal neovascularization.
Main Results:
- Both classic and alternative polarized macrophages exhibited proangiogenic and inflammatory gene/protein profiles.
- Activated macrophages, particularly M(IFNγ and LPS) phenotype from nvAMD patients, demonstrated proangiogenic effects ex vivo and in vivo.
Conclusions:
- Activated human macrophages, especially M(IFNγ and LPS) phenotype from nvAMD patients, are implicated in nvAMD pathogenesis.
- Further research is needed to explore activated macrophages as potential therapeutic targets for nvAMD.
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