Neutrophil Extracellular Traps: Current Perspectives in the Eye

Abstract

Neutrophil extracellular traps (NETs) have been the subject of research in the field of innate immunity since their first description more than a decade ago. Neutrophils are the first cells recruited at sites of inflammation, where they perform their specific functions, including the release of NETs, which consist of web-like structures composed of granule proteins bound to decondensed chromatin fibres. This process has aroused interest, as it contributes to understanding how pathogenic microorganisms are contained, but they are also associated with pathophysiological processes of a wide range of diseases. Currently, there are growing reports of new molecules involved in the formation and release of NETs. However, whether the release of NETs contributes to eye diseases remains unclear. For this reason, the overall aim of this review is to gather current data of recent research in the ophthalmology field, where there is still much to discover.

The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens

“…It is commonly accepted that ROS are essential to initiate the formation of extracellular traps by activated neutrophils during infection and inflammation [ 124 ]. NETs represent a powerful and specific tool that allows neutrophils to capture and effectively destroy a broad range of pathogens while minimizing damage to host tissue [ 125 ]. They are characterized as extracellular fibrous structures composed of decondensed intracellular DNA associated with antimicrobial proteins such as neutrophil elastase (NE), lactoferrin, MPO, calprotectin and cathepsin G, and histones and some other cytoplasmic proteins [ 109 , 126 ] (Fig.…”

“…First, NET formation was considered a particular form of cell death (“NETosis”) and thus, to be suicidal to neutrophils. This view, however, has been challenged by recent reports, which found that some neutrophils can survive this event and remain structurally intact, suggesting two mechanisms of NETosis: suicidal and vital [ 125 , 131 ].…”

“…In suicidal NETosis, intracellular NET formation is followed by the rupture of the cell envelope resulting in the NET release into the extracellular surroundings, but also in neutrophil death and the loss of viable cell functions, such as chemotaxis and the ability to phagocytize pathogens. In contrast, vital NETosis ends up with the production of a DNA-filled vesicle that fuses with the outer membrane to release NETs [ 125 , 131 ]. Since the plasma membrane remains intact, neutrophils that undergo vital NETosis remain temporarily functional as anuclear cytoplasts, still able to multitask.…”

Neutrophils and Neutrophil Extracellular Traps Regulate Immune Responses in Health and Disease

“…Surprisingly, unlike many other crystalline particles, the ingestion of hemozoin crystals by neutrophils does not induce NETs formation [ 8 ]. Next, Estúa-Acosta et al challenge the idea that the eye is an immune-privileged organ and provide evidence of NETs and their implication in pathophysiology in infectious keratitis, the leading cause of monocular blindness as well as non-infectious eye diseases [ 9 ]. Meanwhile, Magán-Fernández et al summarize the current knowledge about the role of NETs in the pathogenesis of periodontitis [ 10 ].…”

“…In this issue, Manda-Handzlik and Demkow discuss the contribution of NETs in different pathological conditions affecting the central nervous system, e.g., trauma, neurodegeneration, and autoimmune diseases [ 3 ]. Estúa-Acosta et al discuss the contribution of NETs in eye physiology, e.g., eye rheum formation as well as pathophysiological conditions, e.g., dry eye disease, corneal injuries like alkali burn, uveitis, diabetic retinopathy, and age-related macular degeneration [ 9 ]. Interestingly, the same mechanism was found to be responsible for uveitis in large animals.…”