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Updated: Apr 6, 2026
Quantification of Vascular Parameters in Whole Mount Retinas of Mice with Non-Proliferative and Proliferative Retinopathies
Published on: March 12, 2022
M2 Macrophages Enhance Pathological Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy
Yedi Zhou1, Shigeo Yoshida1, Shintaro Nakao1
1Department of Ophthalmology Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Purpose:
To investigate the roles played by M2 macrophages in a mouse model of oxygen-induced retinopathy (OIR).
Methods:
Oxygen-induced retinopathy was induced in C57BL/6J mice by exposing postnatal day seven (P7) pups to 75% oxygen and then returning them to room air at P12. Real-time RT-PCR and immunofluorescence staining were used to assess the levels and distributions of different macrophage markers. Bone marrow-derived M1 and M2 macrophages and mannosylated clodronate liposomes (MCLs) were injected into the vitreous on P12 to examine the effects at P17. M2 macrophages were cocultured with human retinal endothelial cells (HRECs) to examine their effects on proliferation and tube formation.
Results:
The results showed that the M2 macrophages, rather than M1 phenotype, were highly expressed in OIR mice. The number of M2 macrophages had increased significantly at P17, and the increase was closely associated with the presence of neovascular tufts in the OIR retinas. Selective depletion of M2 macrophages suppressed the pathological neovascularization and promoted physiological revascularization. In contrast, intravitreal injection of bone marrow-derived M2 macrophages or the culture supernatants promoted pathological neovascularization and inhibited physiological revascularization. In an in vitro coculture system, M2-polarized macrophages significantly promoted proliferation and tube formation of HRECs.
Conclusions:
These results indicated that M2 macrophages, rather than M1, play an important role in promoting retinal pathological neovascularization probably by producing secreted factors. Thus, targeting M2 macrophages could be a potential therapeutic option for inhibiting retinal pathological neovascularization.
Insights
M2 macrophages, not M1, drive pathological neovascularization in oxygen-induced retinopathy (OIR). Targeting M2 macrophages may offer a novel therapeutic strategy for OIR treatment.
Area of Science:
- Immunology
- Ophthalmology
- Vascular Biology
Background:
- Oxygen-induced retinopathy (OIR) is a common cause of vision impairment.
- Macrophage polarization plays a critical role in inflammatory and neovascular diseases.
- The specific role of M2 macrophages in OIR pathogenesis remains unclear.
Purpose of the Study:
- To investigate the role of M2 macrophages in a mouse model of oxygen-induced retinopathy (OIR).
- To determine if M2 macrophages promote or inhibit pathological neovascularization in OIR.
Main Methods:
- Oxygen-induced retinopathy (OIR) was induced in C57BL/6J mice.
- Macrophage markers were assessed using RT-PCR and immunofluorescence.
- M2 macrophages were depleted or administered intravitreally.
- M2 macrophages were co-cultured with human retinal endothelial cells (HRECs) in vitro.
Main Results:
- M2 macrophages, not M1, were significantly upregulated in OIR retinas.
- Increased M2 macrophages correlated with neovascular tufts.
- Depletion of M2 macrophages reduced pathological neovascularization and enhanced physiological revascularization.
- M2 macrophages promoted HREC proliferation and tube formation in vitro.
Conclusions:
- M2 macrophages, rather than M1, are key drivers of retinal pathological neovascularization in OIR.
- M2 macrophages likely exert their pro-angiogenic effects through secreted factors.
- Targeting M2 macrophages represents a promising therapeutic avenue for OIR.
