June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Natural killer cells cooperate with neutrophils to suppress pathological angiogenesis in neovascular age-related macular degeneration
Author Affiliations & Notes
  • Xue Dong
    Tianjin Medical University, Tianjin, China
    Tianjin Medical University General Hospital, Tianjin, Tianjin, China
  • Yinting Song
    Tianjin Medical University, Tianjin, China
    Tianjin Medical University General Hospital, Tianjin, Tianjin, China
  • Xiaohong Wang
    Tianjin Medical University, Tianjin, China
    Tianjin Medical University General Hospital, Tianjin, Tianjin, China
  • Hua Yan
    Tianjin Medical University, Tianjin, China
    Tianjin Medical University General Hospital, Tianjin, Tianjin, China
  • Footnotes
    Commercial Relationships   Xue Dong None; Yinting Song None; Xiaohong Wang None; Hua Yan None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3908. doi:
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      Xue Dong, Yinting Song, Xiaohong Wang, Hua Yan; Natural killer cells cooperate with neutrophils to suppress pathological angiogenesis in neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3908.

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

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Abstract

Purpose : Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Inflammation controls neovascularization and the progression of AMD, but the precise immune components governing this process remain poorly understood. Natural killer (NK) cells respond rapidly to inflammatory signals and are among the first cell types to reach the target organ. They have the ability to recognize and kill foreign, infected, and malignant cells. However, the potential involvement of NK cells and their impact on AMD are yet to be defined.

Methods : We used single-cell RNA-seq, flow cytometry, and immunofluorescence staining to investigate the involvement of NK cells in nvAMD using samples from AMD patients and a mouse model of CNV. The role of NK cells was examined using antibody-mediated depletion methods and genetic models. Olink high-throughput proteomic analysis, NK cell transplantation experiments, and cell-chat assay were used to study the mechanism of NK cell recruitment. Flow cytometry and in vitro experiments with human NK-92 cells were used to study the mechanism of NK cell activation.

Results : We identified NK cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization lesions in CNV mouse model and patients with nvAMD. NK cells suppress pathological angiogenesis via clearance of senescent vasculature, a process that requires neutrophil extracellular traps (NETs) and is suppressed in the elderly. Mechanistically, the release of NETs results from NKG2D-dependent NK cell–mediated cytotoxicity against NKG2D ligand-bearing neutrophils at CNV lesions. Additionally, expansion of NK cells by IL-2 complex improved CNV formation.

Conclusions : Collectively, our results revealed a previously unrecognized role of NK cells to suppress nvAMD progression, implying NK cells as a potential target for future design of immune therapy for patients with nvAMD.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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