Myeloid lineage contributes to pathological choroidal neovascularization formation via SOCS3

Tianxi Wang, Pingzhu Zhou, Xuemei Xie, Yohei Tomita, Steve Cho, Demetrios Tsirukis, Enton Lam, Hongbo Robert Luo, Ye Sun

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Background: Pathological neovascularization in neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. Increasing evidence shows that cells of myeloid lineage play important roles in controlling pathological endothelium formation. Suppressor of cytokine signaling 3 (SOCS3) pathway has been linked to neovascularization. Methods: We utilised a laser-induced choroidal neovascularization (CNV) mouse model to investigate the neovascular aspect of human AMD. In several cell lineage reporter mice, bone marrow chimeric mice and Socs3 loss-of-function (knockout) and gain-of-function (overexpression) mice, immunohistochemistry, confocal, and choroidal explant co-culture with bone marrow-derived macrophage medium were used to study the mechanisms underlying pathological CNV formation via myeloid SOCS3. Findings: SOCS3 was significantly induced in myeloid lineage cells, which were recruited into the CNV lesion area. Myeloid Socs3 overexpression inhibited laser-induced CNV, reduced myeloid lineage-derived macrophage/microglia recruitment onsite, and attenuated pro-inflammatory factor expression. Moreover, SOCS3 in myeloid regulated vascular sprouting ex vivo in choroid explants and SOCS3 agonist reduced in vivo CNV. Interpretation: These findings suggest that myeloid lineage cells contributed to pathological CNV formation regulated by SOCS3. Funding: This project was funded by NIH/NEI (R01EY030140, R01EY029238), BrightFocus Foundation, American Health Assistance Foundation (AHAF), and Boston Children's Hospital Ophthalmology Foundation for YS and the National Institutes of Health/National Heart, Lung and Blood Institute (U01HL098166) for PZ.

Original languageEnglish
Article number103632
JournalEBioMedicine
Volume73
DOIs
Publication statusPublished - 2021 Nov
Externally publishedYes

Keywords

  • Age-related macular degeneration
  • Choroidal neovascularization
  • Myeloid lineage
  • Pathological endothelium formation
  • SOCS3

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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