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Updated: Jun 12, 2026
Assessment of Vascular Regeneration in the CNS Using the Mouse Retina
Published on: June 23, 2014
M2 Macrophage-Derived Migrasomes Mediate Ischaemia-Induced Retinal Neovascularization by Targeting TREM2
Bingyan Li1,2, Junyu Chen1,2, Junye Zhu1,2
1Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Abstract:
Retinal neovascular diseases are leading causes of global blindness. Migrasomes, organelles released during cell migration, play a role in intercellular communication and are present in M2 macrophages, which are critical to the pathology of retinal neovascular diseases. This study investigates the involvement of M2 macrophage-derived migrasomes in ischaemia-induced retinal neovascularization (RNV). Migrasomes are isolated from macrophages and characterized by Western blotting and transmission electron microscopy. Compared with controls, M2 macrophage-derived migrasomes significantly enhance human retinal microvascular endothelial cell (HREC) functions by Cell Counting Kit-8, transwell, and tube formation assays, and markedly contribute to the pathological retinal angiogenesis of oxygen-induced retinopathy (OIR) mice. Triggering receptor expressed on myeloid cells 2 (TREM2) is selected as the potential downstream target of M2 macrophage-derived migrasomes by proteomic analysis. Moreover, the depletion of M2 macrophages in OIR retinas reduces the levels of migrasomes and TREM2. BTC and PLA1A overexpression in HRECs could attenuate decreased HREC functions induced by sh-TREM2 M2 macrophage-derived migrasomes. These findings demonstrate that TREM2-enriched M2 macrophage-derived migrasomes contribute to pathological RNV in vivo and positively regulate HREC functions in vitro through targeting TREM2-BTC/PLA1A, which may serve as biomarkers and therapeutic targets for retinal neovascular diseases.
Insights
M2 macrophage-derived migrasomes enhance retinal neovascularization by targeting TREM2-BTC/PLA1A. These migrasomes may serve as novel biomarkers and therapeutic targets for retinal neovascular diseases.
Area of Science:
- Ophthalmology
- Cell Biology
- Immunology
Background:
- Retinal neovascular diseases are a major cause of blindness.
- M2 macrophages and their released migrasomes are implicated in retinal neovascularization.
- Intercellular communication via migrasomes is crucial in disease pathology.
Purpose of the Study:
- To investigate the role of M2 macrophage-derived migrasomes in ischemia-induced retinal neovascularization (RNV).
- To identify downstream targets of these migrasomes in regulating retinal angiogenesis.
- To explore potential therapeutic strategies for retinal neovascular diseases.
Main Methods:
- Isolation and characterization of migrasomes from M2 macrophages using Western blotting and transmission electron microscopy.
- In vitro assays (Cell Counting Kit-8, transwell, tube formation) to assess human retinal microvascular endothelial cell (HREC) function.
- Proteomic analysis to identify TREM2 as a downstream target.
- Oxygen-induced retinopathy (OIR) mouse model to study in vivo effects.
- Depletion of M2 macrophages and gene manipulation (overexpression/shRNA) in HRECs.
Main Results:
- M2 macrophage-derived migrasomes significantly enhanced HREC functions in vitro.
- These migrasomes markedly contributed to pathological retinal angiogenesis in OIR mice.
- Proteomic analysis identified TREM2 as a key target, with its levels reduced upon M2 macrophage depletion.
- BTC and PLA1A overexpression in HRECs attenuated the negative effects of TREM2 knockdown.
Conclusions:
- TREM2-enriched M2 macrophage-derived migrasomes promote pathological RNV in vivo and enhance HREC functions in vitro.
- The mechanism involves targeting the TREM2-BTC/PLA1A pathway.
- M2 macrophage-derived migrasomes represent potential biomarkers and therapeutic targets for retinal neovascular diseases.
