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Updated: Mar 7, 2026
Monitoring Dynamic Growth of Retinal Vessels in Oxygen-Induced Retinopathy Mouse Model
Published on: April 2, 2021
PEDF mediates pathological neovascularization by regulating macrophage recruitment and polarization in the mouse
Sha Gao1, Changwei Li2, Yanji Zhu1
1Department of Ophthalmology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People's Republic of China.
Abstract:
Macrophages have been demonstrated to play a proangiogenic role in retinal pathological vascular growth. Pigment epithelium-derived factor (PEDF) works as a powerful endogenous angiogenesis inhibitor, but its role in macrophage recruitment and polarization is largely unknown. To explore the underlying mechanisms, we first evaluated macrophage polarization in the retinas of the oxygen-induced retinopathy (OIR) mouse model. Compared to that in normal controls, M1- and M2-like macrophages were all abundantly increased in the retinas of OIR mice. In addition, both M1 and M2 subtypes significantly promoted neovascularization in vitro and in vivo. In addition, we found that PEDF inhibited retinal neovascularization by dampening macrophage recruitment and polarization. Furthermore, PEDF inhibited macrophage polarization through adipose triglyceride lipase (ATGL) by regulating the activation of MAPKs and the Notch1 pathway, as we found that the phosphorylation of MAPKs, including p38MAPK, JNK and ERK, as well as the accumulation of Notch1 were essential for hypoxia-induced macrophage polarization, while PEDF significantly dampened M1 subtype-related iNOS and M2 subtype-related Arg-1 expression by inhibiting hypoxia-induced activation of Notch1 and MAPKs through ATGL. These findings reveal a protective role of PEDF against retinal neovascularization by regulating macrophage recruitment and polarization.
Insights
Pigment epithelium-derived factor (PEDF) inhibits pathological retinal neovascularization by reducing macrophage recruitment and polarization. PEDF regulates macrophage polarization via adipose triglyceride lipase (ATGL), impacting key signaling pathways.
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- Macrophages contribute to pathological retinal neovascularization.
- Pigment epithelium-derived factor (PEDF) is an endogenous angiogenesis inhibitor.
- PEDF's role in macrophage recruitment and polarization is not well understood.
Purpose of the Study:
- To investigate the role of PEDF in regulating macrophage polarization in oxygen-induced retinopathy (OIR).
- To elucidate the mechanisms by which PEDF influences macrophage polarization and retinal neovascularization.
Main Methods:
- Utilized the oxygen-induced retinopathy (OIR) mouse model.
- Analyzed macrophage polarization (M1 and M2 subtypes) in retinal tissues.
- Investigated the involvement of adipose triglyceride lipase (ATGL), MAPKs, and Notch1 pathways.
Main Results:
- Both M1 and M2 macrophages were increased in OIR retinas and promoted neovascularization.
- PEDF inhibited retinal neovascularization by reducing macrophage recruitment and polarization.
- PEDF suppressed hypoxia-induced macrophage polarization via ATGL, inhibiting MAPK and Notch1 activation.
Conclusions:
- PEDF exerts a protective effect against retinal neovascularization.
- PEDF regulates macrophage recruitment and polarization, dampening proangiogenic M1 and M2 subtypes.
- The PEDF-ATGL axis is crucial for controlling macrophage polarization and retinal angiogenesis.
