Lymphocytic microparticles suppress retinal angiogenesis via targeting Müller cells in the ischemic retinopathy mouse model
- CHU Sainte-Justine Research Center, Montreal, Quebec (Canada)
- Departments of Pharmacology and Physiology, University of Montreal, Montreal, Quebec (Canada)
Highlights: F0B7 • LMPs possess strong angiogenesis-inhibiting properties. F0B7 • LMPs suppress Müller cell-derived angiogenic/chemoattractant factors. F0B7 • LMPs attenuate pathological retinal NV and the infiltration of macrophages in vivo. F0B7 • LMPs downregulate ERK1/2 and HIF-1α both in vitro and in vivo. Retinopathy of prematurity (ROP) is the primary cause of visual impairment and vision loss in premature infants, which results from the formation of aberrant retinal neovascularization (NV). An emerging body of evidence has shown that Müller cells are the predominant source of vascular endothelial growth factor (VEGF), which also serves as a chemoattractant for monocyte/macrophage lineage. The recruitment of macrophages is increased during retinal NV, and they exert a pro-angiogenic role in ROP. We have shown that lymphocytic microparticles (microvesicles; LMPs) derived from apoptotic human T lymphocytes possess strong angiogenesis-inhibiting properties. Here, we investigated the effect of LMPs on the chemotactic capacity of Müller cells in vitro using rat Müller cell rMC-1 and mouse macrophage RAW 264.7. In addition, the impact of LMPs was determined in vivo using a mouse model of oxygen-induced ischemic retinopathy (OIR). The results revealed that LMPs were internalized by rMC-1 and reduced their cell proliferation dose-dependently without inducing cell apoptosis. LMPs inhibited the chemotactic capacity of rMC-1 on RAW 264.7 via reducing the expression of VEGF. Moreover, LMPs attenuated pathological retinal NV and the infiltration of macrophages in vivo. LMPs downregulated ERK1/2 and HIF-1α both in vitro and in vivo. These findings expand our understanding of the effects of LMPs, providing evidence of LMPs as a promising therapeutic approach for the treatment of retinal NV diseases.
- OSTI ID:
- 23195363
- Journal Information:
- Experimental Cell Research, Vol. 399, Issue 2; Other Information: Copyright (c) 2021 The Author(s). Published by Elsevier Inc.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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