ArticleThe ocular surface2019
Neutrophil extracellular traps (NETs) contribute to pathological changes of ocular graft-vs.-host disease (oGVHD) dry eye: Implications for novel biomarkers and therapeutic strategies.
Article in The ocular surface, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 52 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I/II Randomized, Placebo-controlled, Double-Blind, Single-Center, Tolerability and Preliminary Efficacy Clinical Trial of Intravenous Immunoglobulin (IVIG) Eye Drops in Patients With Dry Eye Disease
2177GCCC: Identifying Novel Treatment Targets and Biomarkers for Ocular Surface Disease in Patients With Ocular Graft vs Host Disease (oGVHD) a Biobank Study
Who cites it
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- Pooled it
- Role of Neutrophils on the Ocular Surface.International journal of molecular sciences · 2021Pooled it
- Pegtarazimod limits acute graft-versus-host disease mortality and severity in mice and is tolerated in patients.The Journal of clinical investigation · 2026Article
- Advances in dry eye disease: from immunopathological mechanisms to emerging ophthalmic drug delivery systems.Frontiers in medicine · 2026Review
- Platelet-Derived Growth Factor Isoform Imbalance Is Associated with Innate Inflammation and Corneal Epitheliopathy in Dry Eye Disease.Ophthalmic research · 2026Article
- Neutrophil Extracellular Traps in Dry Eye: A Comprehensive Review of Pathogenic Mechanisms and Implications for Targeted Therapy.International journal of general medicine · 2026Review
- Tear fluid derived extracellular vesicles for new biomarker discovery.The ocular surface · 2025Review
- Longitudinal Tear Cytokine Biomarkers: An Analysis from the Close Assessment and Testing for Chronic Graft-Versus-Host Disease (CATCH) Protocol.Transplantation and cellular therapy · 2025Observational
- [Ocular graft versus host disease].Die Ophthalmologie · 2025Review
- Lipocalin-2 and intestinal diseases.World journal of gastroenterology · 2024Review
- Advances in the ocular complications after hematopoietic stem cell transplantation.Annals of hematology · 2024Review
- Mesenchymal Stem Cells-Derived Exosomal miR-223-3p Alleviates Ocular Surface Damage and Inflammation by Downregulating Fbxw7 in Dry Eye Models.Investigative ophthalmology & visual science · 2024Article
- The Preventive and Therapeutic Effects of Acute and Severe Inflammatory Disorders with Heparin and Heparinoid.Biomolecules · 2024Review
- Article
- Immunopathological mechanisms and clinical manifestations of ocular graft-versus-host disease following hematopoietic stem cell transplantation.Bone marrow transplantation · 2024Review
- The Necroptosis Pathway Is Upregulated in the Cornea in Mice With Ocular Graft-Versus-Host Disease.Investigative ophthalmology & visual science · 2024Article
- Rapid NETosis Is an Effector Mechanism to Combat Ocular Herpes Infection.Investigative ophthalmology & visual science · 2024Article
- The Yin and Yang of non-immune and immune responses in meibomian gland dysfunction.The ocular surface · 2024Article
- Ophthalmic Manifestations in Patients with Blood Malignancies.Hematology reports · 2024Review
- [Clinical study of the cytokine panel in the diagnosis of ocular chronic graft-versus-host disease].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo investigate the role of neutrophil extracellular traps (NETs) and NET-associated proteins in the pathogenesis of oGVHD and whether dismantling of NETs with heparin reduces those changes.
methodsOcular surface washings from oGVHD patients and healthy subjects were analyzed. Isolated peripheral blood human neutrophils were stimulated to generate NETs and heparinized NETs. We performed in vitro experiments using cell lines (corneal epithelial, conjunctival fibroblast, meibomian gland (MG) epithelial and T cells), and in vivo experiments using murine models, and compared the effects of NETs, heparinized NETs, NET-associated proteins and neutralizing antibodies to NET-associated proteins.
resultsNeutrophils, exfoliated epithelial cells, NETs and NET-associated proteins (extracellular DNA, Neutrophil Elastase, Myeloperoxidase, Oncostatin M (OSM), Neutrophil gelatinase-associated lipocalin (NGAL) and LIGHT/TNFSF14) are present in ocular surface washings (OSW) and mucocellular aggregates (MCA). Eyes with high number of neutrophils in OSW have more severe signs and symptoms of oGVHD. NETs (and OSM) cause epitheliopathy in murine corneas. NETs (and LIGHT/TNFSF14) increase proliferation of T cells. NETs (and NGAL) inhibit proliferation and differentiation of MG epithelial cells. NETs enhance proliferation and myofibroblast transformation of conjunctival fibroblasts. Sub-anticoagulant dose Heparin (100 IU/mL) dismantles NETs and reduces epithelial, fibroblast, T cell and MG cell changes induced by NETs.
conclusionNETs and NET-associated proteins contribute to the pathological changes of oGVHD (corneal epitheliopathy, conjunctival cicatrization, ocular surface inflammation and meibomian gland disease). Our data points to the potential of NET-associated proteins (OSM or LIGHT/TNFSF14) to serve as biomarkers and NET-dismantling biologics (heparin eye drops) as treatment for oGVHD.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.