Altered activation state of circulating neutrophils in patients with neovascular age-related macular degeneration

Abstract

BackgroundNeutrophil dysfunction plays a key role in the development of diseases characterized by inflammation and angiogenesis. Here, we studied the systemic expression of neutrophil markers reflecting activation, adhesion, and resolution of inflammation in patients with neovascular age-related macular degeneration (AMD).ResultsThis was a prospective case-control study of patients with neovascular AMD and age-matched healthy control individuals. Patients were recruited from an outpatient program, and control individuals were recruited amongst patients’ relatives. Current smokers and individuals with either active immune-disease or ongoing cancer were not included, as these factors are known to affect neutrophil function. Fresh-drawn venous blood was processed for flow cytometric analysis of neutrophil markers. We determined percentages of positive cells and compared expression levels using fluorescence intensity measures. We found conditional differences on marker expression between patients with neovascular AMD (n = 29) and controls (n = 28): no differences were found when looking broadly, but several differences emerged when focusing on non-smokers. Here, patients with neovascular AMD had increased expression of the activity marker cluster of differentiation (CD) 66b (P = 0.003; Mann-Whitney U test), decreased expression of adhesion marker CD162 (P = 0.044; Mann-Whitney U test), and lower expression of the resolution of inflammation marker C-X-C chemokine receptor 2 (P = 0.044; Mann-Whitney U test).ConclusionsWe present novel evidence suggesting that the activity of circulating neutrophils, sensitive to smoking, may differ in patients with neovascular AMD.

Neutrophil‐to‐lymphocyte ratio in age‐related macular degeneration: a systematic review and meta‐analysis

“…Clinical studies point that these neutrophils may also be fundamentally different in patients with neovascular AMD (Krogh Nielsen et al. ), since neutrophils from patients express more of the surface marker CD66b and less of the surface markers CD162 and CXCR2 (Krogh Nielsen et al. ).…”

Effect of aging and lifestyle on photoreceptors and retinal pigment epithelium: cross-sectional study in a healthy Danish population

“…These aspects remain incompletely understood; however, two important functional pathways provide an important theoretical framework. First, smoking mediates a substantial amount of their systemic toxicity though increased systemic reactive oxygen species [34–37]. Second, blood flow studies find decreased retinal blood flow due to increased vascular resistance [38–40], which may exert further pressure on the age-related increased metabolic load on RPE cells.…”

Patients with a fast progression profile in geographic atrophy have increased CD200 expression on circulating monocytes

“…10,11 These infiltrating cells and the broad alterations of systemic immune cells suggests the involvement of the adaptive immune system in AMD and supports the notion of AMD as a systemic disease. In patients with neovascular AMD we previously found neutrophils with an altered activation state, 12 lower frequency of T-helper 1 cell 13 and aged phenotype of cytotoxic T-cells. 14 Furthermore, natural killer cells are demonstrated to promote CNV formation, 15 and B cells from donors with AMD tend to be more sensitive to antigen-stimulation.…”