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Published on: February 28, 2017
Notch signaling regulates M2 type macrophage polarization during the development of proliferative vitreoretinopathy
Jingjing Zhang1, Qingjun Zhou2, Gongqiang Yuan1
1Shandong Eye Hospital, Shandong Eye Institute, Shandong Academy of Medical Sciences, Jinan, China.
Abstract:
Macrophages play an important role in the pathogenesis of proliferative vitreoretinopathy (PVR). M2 macrophages can promote tissue remodeling and repair. In this study, CD206 positive M2 type macrophages were found in preretinal fibrous membranes of the mouse model of PVR induced by the intravitreal injection of retinal pigment epithelial (RPE) cells. Notch signaling determines M2 macrophage polarization. The specific inhibition of Notch signaling pathway by the intravitreal injection of γ-secretase inhibitor DAPT attenuated RPE cells-induced PVR formation as demonstrated by the decreased expression of α-SMA, and inhibited M2 type macrophage infiltation as demonstrated by the decreased expression of Arg-1. Notch signaling may modulate PVR formation by regulating M2 type macrophage polarization.
Insights
Notch signaling drives M2 macrophage polarization, a key factor in proliferative vitreoretinopathy (PVR). Inhibiting Notch signaling reduces PVR development and M2 macrophage infiltration, suggesting a therapeutic target for PVR.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Macrophages are implicated in proliferative vitreoretinopathy (PVR) pathogenesis.
- M2 macrophages contribute to tissue remodeling and repair processes.
- CD206-positive M2 macrophages are present in preretinal membranes in a mouse model of PVR.
Purpose of the Study:
- To investigate the role of Notch signaling in M2 macrophage polarization in PVR.
- To determine if inhibiting Notch signaling affects PVR formation and M2 macrophage infiltration.
Main Methods:
- Induction of PVR in a mouse model via intravitreal injection of retinal pigment epithelial (RPE) cells.
- Administration of a γ-secretase inhibitor (DAPT) to block Notch signaling.
- Assessment of PVR markers (α-SMA) and M2 macrophage markers (CD206, Arg-1).
Main Results:
- Inhibition of Notch signaling with DAPT reduced PVR formation.
- DAPT treatment decreased the expression of α-SMA, a marker of fibrosis.
- M2 type macrophage infiltration was inhibited, evidenced by reduced Arg-1 expression.
Conclusions:
- Notch signaling pathway plays a crucial role in modulating PVR formation.
- Notch signaling influences PVR by regulating M2 type macrophage polarization.
- Targeting Notch signaling may offer a therapeutic strategy for PVR.
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