期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 20, 页码 -出版社
MDPI
DOI: 10.3390/ijms232012549
关键词
age-related macular degeneration; blood outgrowth endothelial cells; sprouting angiogenesis; single-cell transcriptome; endothelial cell states
资金
- Ministry of Education, Singapore [MOE2018-T2-1-042, RG88/21]
- Ministry of Education, Singapore
- SERI-IMCB Program in Retinal Angiogenic Diseases (SIPRAD) from Agency for Science, Technology and Research, Singapore [SPF2014/002]
- Nanyang President's Graduate Scholarship
Age-related macular degeneration is a common cause of visual impairment in older populations worldwide. Wet AMD, the most common subtype, is characterized by pathological angiogenesis and is typically treated with anti-vascular endothelial growth factor therapy. However, long-term prevention of visual decline is still a challenge. Researchers have identified potential VEGF-independent pathways involved in wet AMD pathogenesis, including extracellular matrix remodeling, interleukin signaling, and amino acid metabolism.
Age-related macular degeneration (AMD) is a global leading cause of visual impairment in older populations. 'Wet' AMD, the most common subtype of this disease, occurs when pathological angiogenesis infiltrates the subretinal space (choroidal neovascularization), causing hemorrhage and retinal damage. Gold standard anti-vascular endothelial growth factor (VEGF) treatment is an effective therapy, but the long-term prevention of visual decline has not been as successful. This warrants the need to elucidate potential VEGF-independent pathways. We generated blood out-growth endothelial cells (BOECs) from wet AMD and normal control subjects, then induced angiogenic sprouting of BOECs using a fibrin gel bead assay. To deconvolute endothelial heterogeneity, we performed single-cell transcriptomic analysis on the sprouting BOECs, revealing a spectrum of cell states. Our wet AMD BOECs share common pathways with choroidal neovascularization such as extracellular matrix remodeling that promoted proangiogenic phenotype, and our 'activated' BOEC subpopulation demonstrated proinflammatory hallmarks, resembling the tip-like cells in vivo. We uncovered new molecular insights that pathological angiogenesis in wet AMD BOECs could also be driven by interleukin signaling and amino acid metabolism. A web-based visualization of the sprouting BOEC single-cell transcriptome has been created to facilitate further discovery research.
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