July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
The role and mechanism of polarized macrophages regulating bone marrow-derived cells in the oxygen-induced retinal neovascularization
Author Affiliations & Notes
  • Changmei Guo
    Department of Ophthalmology, XIJING HOSPITAL, XI'AN, SHAANXI, China
  • Yafen Wang
    Department of Ophthalmology, XIJING HOSPITAL, XI'AN, SHAANXI, China
  • Yusheng Wang
    Department of Ophthalmology, XIJING HOSPITAL, XI'AN, SHAANXI, China
  • Footnotes
    Commercial Relationships   Changmei Guo, None; Yafen Wang, None; Yusheng Wang, None
  • Footnotes
    Support  National Natural Science Fund of China, NO. 81470655
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4075. doi:
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      Changmei Guo, Yafen Wang, Yusheng Wang; The role and mechanism of polarized macrophages regulating bone marrow-derived cells in the oxygen-induced retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4075.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To investigate the role and mechanism played by polarized macrophages regulating bone marrow(BM)-derived cells (BMCs) in the oxygen-induced retinopathy (OIR).

Methods : BMCs from green fluorescent protein (GFP) transgenic mice were transplanted into postnatal day (P) 1 C57BL/6J mice after irradiation. The mice were exposed to 75 % oxygen from P7 to P12 to initiate OIR. The macrophages were depleted by injection of clodronate-liposomes intraperitoneally. BM-derived M1 and M2 macrophages were injected into the vitreous at P12 to examine the effects at P17. Retinal flatmounts were performed to analyze the severity of retinal neovascularization (NV) and BMCs recruitment. In vitro, we used conditional medium (CM) from M1 or M2 macrophages to culture BM-derived mesenchymal stem cells (BM-MSCs) to examine their effects on differentiation and migration.

Results : The results showed that macrophage depletion reduced retinal avascular area, NV tufts and the migration of transplanted BMCs into the retina at P17. Furthermore, after injection of M2 macrophages, the area of retinal NV at P17 increased compared with the injection of M1 macrophages or macrophage depletion group. Meanwhile, there were many GFP-positive BMCs in the retina at P17, indicating that different subtypes of macrophages could recruit BMCs. Similarly, in vitro the BM-MSCs showed enhanced CD31-positive endothelial cells and α-SMA-positive smooth muscle cells in the presence M2-CM than M1-CM. And BM-MSCs migration in a transwell assay indicated that the microenvironment formed by M1-CM secretion factor has much lower attraction ability to BM-MSCs than M0 or M2-CM. We also found that CXCR4/stromal cell-derived factor-1(SDF-1) and vascular endothelial growth factor (VEGF) signaling might contribute to the migration of BM-MSCs in response to polarized macrophages.

Conclusions : These results indicated that M2 macrophages might play more important role in promoting the vasculogenesis of retinal NV than M1 macrophages and they both participated the recruitment of BMCs in the OIR model, which might be triggered by VEGF and SDF-1 production.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Macrophage depletion reduced retinal avascular area and NV area at P17

Macrophage depletion reduced retinal avascular area and NV area at P17

 

Western blotting indicated that BM-MSCs showed enhanced CD31 and α-SMA in the presence M2-CM than M1-CM

Western blotting indicated that BM-MSCs showed enhanced CD31 and α-SMA in the presence M2-CM than M1-CM

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