Neutrophil serine proteases (NSPs), including neutrophil elastase (NE), proteinase 3, and cathepsin G, are granule-associated enzymes that are secreted from activated neutrophils.
8 In addition to their participation in destruction of bacteria and other pathogens, NSPs have been implicated in many inflammatory human diseases, including chronic obstructive pulmonary disease, cystic fibrosis, acute respiratory distress syndrome,
9 chronic kidney disease, and inflammatory bowel disease.
10,11 In all these conditions, activated neutrophils secrete activated NE, thus driving local inflammation and pathology.
12–15 Some of the inflammatory changes induced by NE in other diseases are similar to what has been identified to play a role in the development of DR, including involvement of nuclear factor-κB (NF-κB), Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), and mitogen-activated protein kinases (MAPKs).
16–18 Additionally, we have recently reported that NE, encoded by the
Elane gene, contributes to the vascular leakage in the early stages of DR, potentially via PAR2, MyD88, and NF-κB signaling.
19 We hypothesize that proteases released from neutrophils, most probably NE, might be the key factors in the pathogenesis of capillary degeneration and in the molecular abnormalities that contribute to the diabetes-associated retinopathy.