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Updated: Feb 17, 2026
Monitoring Dynamic Growth of Retinal Vessels in Oxygen-Induced Retinopathy Mouse Model
Published on: April 2, 2021
Spatial distribution of CD115+ and CD11b+ cells and their temporal activation during oxygen-induced retinopathy in
Claudia Brockmann1,2, Sabrina Dege3, Sergio Crespo-Garcia3
1Department of Ophthalmology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany. claudia.brockmann@charite.de.
Purpose:
The model of oxygen-induced retinopathy (OIR) is widely used to analyze pathomechanisms in retinal neovascularization. Previous studies have shown that macrophages (MP) play a key role in vessel formation in OIR, the influence of microglia (MG) having been discussed. The aim of our study was to analyze the spatial and temporal distribution and activation of MP/MG expressing CD115 and CD11b during the process of neovascularization in OIR.
Methods:
We used MacGreen mice expressing the green fluorescence protein (GFP) under the promoter for CD115. CD115+ cells were investigated in vivo by scanning laser ophthalmoscopy at postnatal days (P) 17 and 21 in MacGreen mice with OIR (75% oxygen from P7 to P12), and were compared to MacGreen room-air controls. In addition MP/MG were examined ex vivo using immunohistochemistry for CD11b+ detection on retinal flatmounts at P14, P17, and P21 of wild type mice with OIR.
Results:
In-vivo imaging revealed the highest density of activated MP/MG in tuft areas at P17 of MacGreen mice with OIR. Tufts and regions with a high density of CD115+ cells were detected close to veins, rather to arteries. In peripheral, fully vascularized areas, the distribution of CD115+ cells in MacGreen mice with OIR was similar to MacGreen room-air controls. Correspondingly, immunohistochemical analyses of retinal flatmounts from wild type mice with OIR induction revealed that the number of CD11b+ cells significantly varies between vascular, avascular, and tuft areas as well as between the retinal layers. Activated CD11b+ cells were almost exclusively found in avascular areas and tufts of wild type mice with OIR induction; here, the proportion of activated cells related to the total number of CD11b+ cells remained stable over the course of time.
Conclusions:
Using two different approaches to monitor MP/MG cells, our findings demonstrated that MP/MG concentrate within pathologically vascularized areas during OIR. We were able to clarify that reactive changes of CD11b+ cell distribution to OIR primarily occur in the deep retinal layers. Furthermore, we found the highest proportion of activated CD11b+ cells in regions with pathologic neovascularization processes. Our findings support previous reports about activated MP/MG guiding revascularization in avascular areas and playing a key role in the formation and regression of neovascular tufts.
Insights
Macrophages and microglia (MP/MG) concentrate in pathological neovascularization areas during oxygen-induced retinopathy (OIR). Activated MP/MG are crucial for guiding revascularization and managing neovascular tuft formation and regression in OIR.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Oxygen-induced retinopathy (OIR) is a key model for studying retinal neovascularization.
- Macrophages (MP) and microglia (MG) are implicated in OIR pathogenesis, but their precise roles require further elucidation.
Purpose of the Study:
- To investigate the spatial and temporal distribution and activation status of CD115 and CD11b expressing MP/MG during OIR.
- To differentiate the roles of MP/MG in neovascularization within the OIR model.
Main Methods:
- In vivo imaging of CD115+ cells in MacGreen mice using scanning laser ophthalmoscopy.
- Ex vivo immunohistochemistry for CD11b+ cells on retinal flatmounts from wild-type mice with OIR.
- Comparison of OIR models with room-air controls.
Main Results:
- Highest density of activated MP/MG observed in neovascular tuft areas at postnatal day 17 in OIR models.
- CD115+ cells were predominantly located near veins, not arteries.
- Activated CD11b+ cells were concentrated in avascular areas and tufts, particularly in deep retinal layers, with stable activation proportions over time.
Conclusions:
- MP/MG cells accumulate in pathologically vascularized regions during OIR.
- Reactive changes in CD11b+ cell distribution are primarily in deep retinal layers.
- Activated MP/MG play a critical role in neovascularization, revascularization, and tuft remodeling in OIR.
