The Noninflammatory Phenotype of Neutrophils From the Closed-Eye Environment: A Flow Cytometry Analysis of Receptor Expression

Abstract

Our results indicate that while tear-film neutrophils are alive, they do not respond to inflammatory stimuli in the same manner as blood-isolated neutrophils. This refractory phenotype may be due to exposure to anti-inflammatory factors present in the tear film.

Frontline Science: Aggregated neutrophil extracellular traps prevent inflammation on the neutrophil-rich ocular surface

“…recently reported that after 7 h of sleep, closed eyes were infiltrated by neutrophils, T cells, and monocytes . The presence of viable neutrophils in tear films was also observed by trypan blue and PI exclusion in another study . These findings along with our observations of eye rheum suggest that viable neutrophils patrol the closed eye and form NETs to expand their reach.…”

“…24 The presence of viable neutrophils in tear films was also observed by trypan blue and PI exclusion in another study. 25 In the evening TF, C5a showed higher values (P < 0.01, Fig. 3B).…”

The role of pro-resolving lipid mediators in ocular diseases

“…The requirement of PMN for normal corneal wound healing and nerve regeneration in acute and self-resolving epithelial injury responses is well established [32, 33]. Multiple lines of evidence also suggest that these wound healing PMN as well as nocturnal tear PMN are a non-inflammatory phenotype [2] that is distinct from stereotypical vascular inflammatory PMN. Unlike LXA 4 's endogenous role in healthy and self-resolving corneal inflammatory-reparative responses, topically added or endogenous LXA 4 in chronic or infectious injuries inhibit recruitment of inflammatory PMN, formation of inflammatory cytokines and chemokines, platelet activating factor and pathological angiogenesis [20, 34, 35, 36].…”

“…Hence, a case can be made that innate, adaptive and reparative immune responses in the visual axis are among the most highly evolved. Sight threatening inflammation could be triggered by routine exposure to microbes, pathogens, irritants, neutrophils (PMN) of nocturnal tears [2] at the ocular surface, or through aberrant immune responses resulting from injury or diseases in the neural retina. However, the transparent visual axis has evolved sophisticated mechanisms to tightly control inflammation, raise the threshold for triggering immune responses, and maintain active immune tolerance.…”

Neutrophil heterogeneity: Bona fide subsets or polarization states?

“…For example, in the oral cavity, 2 different neutrophil populations have been reported in healthy patients, 1 mimicking blood neutrophils and a secondary population referred to as parainflammatory neutrophils that display an intermediate activation phenotype . A similar muted inflammatory neutrophil population has been shown to be present in the tear‐film of the eye . In vitro characterization demonstrated that these cells have impaired activation capacity and do not up‐regulate activation markers upon stimulation .…”