M2 Macrophage-Derived Migrasomes Mediate Ischaemia-Induced Retinal Neovascularization by Targeting TREM2

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.