Neutrophil extracellular traps and immunothrombosis in ocular diseases: Emerging mechanisms, fluid biomarkers, and therapeutic targets

Neutrophil extracellular traps (NETs) are extracellular networks of chromatin, histones, and neutrophil-derived proteins released during immune responses.Although NET formation supports antimicrobial defense, excessive or continuous NET formation may promote sterile inflammation, endothelial damage, vascular leakage and immunothrombosis.There is increasing experimental and clinical evidence implicating NET-associated pathways in ocular disorders such as dry eye disease, ocular graft-vshost disease, infectious keratitis, diabetic retinopathy, glaucoma, and immune-mediated ocular inflammation.This narrative review summarizes the molecular mechanisms regulating NET formation and clearance and examines their putative contribution to ocular surface damage, blood-retinal barrier disruption, microvascular occlusion and neuroinflammation.Considerable attention is paid to NET-related biomarkers found in tears, aqueous humor, vitreous and peripheral blood.These include cell-free DNA, citrullinated histones, and myeloperoxidase-DNA complexes.The limitations of the current methodology, biomarker specificity, and ocular evidence vs systemic disease manifestation are discussed thoroughly.Finally, the review examines emerging therapeutic strategies targeting NET formation, persistence, or downstream tissue injury.These include deoxyribonuclease-based strategies, peptidylarginine deiminase 4 inhibition and modulation of neutrophil-endothelial interactions.More standardized clinical studies are needed to evaluate whether NET-associated biomarkers and therapies can assist precision management of ocular disease.