June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
The roles of SOCS3 in myeloid cell-derived neovascular endothelium formation in a laser-induced choroidal neovascularization mouse model
Author Affiliations & Notes
  • TIANXI WANG
    ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Demetrios Tsirukis
    ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Steve Cho
    ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Ye Sun
    ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   TIANXI WANG, None; Demetrios Tsirukis, None; Steve Cho, None; Ye Sun, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 642. doi:
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      TIANXI WANG, Demetrios Tsirukis, Steve Cho, Ye Sun; The roles of SOCS3 in myeloid cell-derived neovascular endothelium formation in a laser-induced choroidal neovascularization mouse model. Invest. Ophthalmol. Vis. Sci. 2021;62(8):642.

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

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Abstract

Purpose : Pathological choroidal neovascularization (CNV) is a common cause of blindness in age-related macular degeneration (AMD). We aim to investigate the underlying molecular mechanism by identifying a novel immunoregulator suppressor of cytokine signaling 3 (SOCS3) which controls the development of myeloid lineage cells into endothelial cells to form the pathological vascular endothelium using a laser-induced CNV mouse model.

Methods : We generated SOCS3 gain-of-function and loss-of-function mice using the Cre/loxP system to modulate endogenous Socs3 levels. Myeloid and endothelial-specific Cre mice and ROSAmT/mG reporter mice were used to trace the origin of neovascularization in the AMD mouse model. Bone marrow from GFP transgenic mice was injected into irradiated mice. Mature endothelial cell markers CD31 and VWF were used for immunostaining. CNV was quantified using image J. Results are presented as mean ± SEM and were compared using the 2-tailed unpaired t-test. Statistical analyses were performed with GraphPad Prism (v6.0).

Results : Our data showed that bone marrow-derived GFP-positive cells gathered at the neovascularization site, and most of them were Iba-1 positive, which means myeloid cells were involved in CNV. We also found in the endothelial-specific promoter-driven GFP mice with CNV, only partial pathological CNV is GFP positive, indicating that endothelial lineage is not the only origin of pathological CNV. In addition, myeloid specific promoter-driven GFP mice, some of the pathological CNV is GFP positive, indicating that myeloid lineage may contribute to pathological CNV. In laser-induced CNV, myeloid specific deletion of SOCS3 increased CNV by 30-40% (p<0.001, n=40-46 lesions from 10 mice/group), and myeloid specific overexpression of SOCS3 reduced CNV by ~25% (p<0.001, n=30 lesions from 8 mice/group). This data suggests that SOCS3 in myeloid lineage controls pathological CNV formation in the laser-induced CNV.

Conclusions : Our data suggests that the myeloid lineage may contribute to pathological neovascularization and the process was modulated by SOCS3 in neovascular AMD mouse model. This finding provides a novel understanding of pathological neovascularization.

This is a 2021 ARVO Annual Meeting abstract.

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