{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:01:22Z","timestamp":1791846082735,"version":"4.3.4"},"reference-count":187,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,6]],"date-time":"2021-06-06T00:00:00Z","timestamp":1622937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Japanese Ministry of Education, Science, Sports, Culture and Technology","award":["26462668 and 18K09421"],"award-info":[{"award-number":["26462668 and 18K09421"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ocular graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. Ocular GVHD affects recipients\u2019 visual function and quality of life. Recent advanced research in this area has gradually attracted attention from a wide range of physicians and ophthalmologists. This review highlights the mechanism of immune processes and the molecular mechanism, including several inflammation cascades, pathogenic fibrosis, and stress-induced senescence related to ocular GVHD, in basic spectrum topics in this area. How the disease develops and what kinds of cells participate in ocular GVHD are discussed. Although the classical immune process is a main pathological pathway in this disease, senescence-associated changes in immune cells and stem cells may also drive this disease. The DNA damage response, p16\/p21, and the expression of markers associated with the senescence-associated secretory phenotype (SASP) are seen in ocular tissue in GVHD. Macrophages, T cells, and mesenchymal cells from donors or recipients that increasingly infiltrate the ocular surface serve as the source of increased secretion of IL-6, which is a major SASP driver. Agents capable of reversing the changes, including senolytic reagents or those that can suppress the SASP seen in GVHD, provide new potential targets for the treatment of GVHD. Creating innovative therapies for ocular GVHD is necessary to treat this intractable ocular disease.<\/jats:p>","DOI":"10.3390\/ijms22116114","type":"journal-article","created":{"date-parts":[[2021,6,6]],"date-time":"2021-06-06T23:59:55Z","timestamp":1623023995000},"page":"6114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Cascade of Inflammatory, Fibrotic Processes, and Stress-Induced Senescence in Chronic GVHD-Related Dry Eye Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Yoko","family":"Ogawa","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Department of Immunology, School of Medicine, International University of Health and Welfare, Chiba 286-8686, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-7111","authenticated-orcid":false,"given":"Kazuo","family":"Tsubota","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/S0140-6736(09)60237-3","article-title":"Graft-versus-host disease","volume":"373","author":"Ferrara","year":"2009","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.bbmt.2014.12.001","article-title":"National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report","volume":"21","author":"Jagasia","year":"2015","journal-title":"Biol. Blood Marrow Transplant. J. Am. Soc. Blood Marrow Transplant."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.survophthal.2012.08.004","article-title":"Ocular Graft-versus-Host Disease: A Review","volume":"58","author":"Shikari","year":"2013","journal-title":"Surv. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1007\/s00417-019-04301-6","article-title":"Ocular surface system alterations in ocular graft-versus-host disease: All the pieces of the complex puzzle","volume":"257","author":"Giannaccare","year":"2019","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1097\/OPX.0000000000001071","article-title":"A Review of Ocular Graft-Versus-Host Disease","volume":"94","author":"Munir","year":"2017","journal-title":"Optom. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/s41409-018-0340-0","article-title":"Ocular graft-versus-host disease after hematopoietic cell transplantation: Expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT","volume":"54","author":"Inamoto","year":"2019","journal-title":"Bone Marrow Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1136\/bjo.83.10.1125","article-title":"Dry eye after haematopoietic stem cell transplantation","volume":"83","author":"Ogawa","year":"1999","journal-title":"Br. J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1136\/bjophthalmol-2011-300514","article-title":"Comparison of stem cell sources in the severity of dry eye after allogeneic haematopoietic stem cell transplantation","volume":"96","author":"Uchino","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/bmt.2009.312","article-title":"Baseline profiles of ocular surface and tear dynamics after allogeneic hematopoietic stem cell transplantation in patients with or without chronic GVHD-related dry eye","volume":"45","author":"Wang","year":"2010","journal-title":"Bone Marrow Transplant."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1590\/abd1806-4841.20164180","article-title":"Cutaneous graft-versus-host disease after hematopoietic stem cell transplant\u2014A review","volume":"91","author":"Villarreal","year":"2016","journal-title":"An. Bras. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S131","DOI":"10.1016\/S1542-0124(12)70238-0","article-title":"Pathways of corneal and ocular surface inflammation: A perspective from the cullen symposium","volume":"3","author":"McDermott","year":"2005","journal-title":"Ocul. Surf."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1167\/tvst.9.3.29","article-title":"Dupilumab-Associated Mucin Deficiency (DAMD)","volume":"9","author":"Barnett","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_13","first-page":"1","article-title":"Modulation of Conjunctival Goblet Cell Function by Inflammatory Cytokines","volume":"2013","author":"Shatos","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Contreras-Ruiz, L., and Masli, S. (2015). Immunomodulatory Cross-Talk between Conjunctival Goblet Cells and Dendritic Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120284"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/mi.2010.82","article-title":"Homeostatic control of conjunctival mucosal goblet cells by NKT-derived IL-13","volume":"4","author":"Raince","year":"2011","journal-title":"Mucosal Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.exer.2013.11.011","article-title":"Topical interferon-gamma neutralization prevents conjunctival goblet cell loss in experimental murine dry eye","volume":"118","author":"Zhang","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_17","first-page":"23","article-title":"Regulation of the inflammatory component in chronic dry eye disease by the eye-associated lymphoid tissue (EALT)","volume":"45","author":"Knop","year":"2010","journal-title":"Dev. Ophthal."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Steven, P., Schwab, S., Kiesewetter, A., Saban, D.R., Stern, M.E., and Gehlsen, U. (2020). Disease-Specific Expression of Conjunctiva Associated Lymphoid Tissue (CALT) in Mouse Models of Dry Eye Disease and Ocular Allergy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207514"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.brainresbull.2009.10.001","article-title":"Innate immunity of the ocular surface","volume":"81","author":"Ueta","year":"2010","journal-title":"Brain Res. Bull."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jtos.2012.12.002","article-title":"Dry Eye Disease and Microbial Keratitis: Is There a Connection?","volume":"11","author":"Narayanan","year":"2013","journal-title":"Ocul. Surf."},{"key":"ref_22","first-page":"111","article-title":"A significant role of stromal fibroblasts in rapidly progressive dry eye in patients with chronic GVHD","volume":"42","author":"Ogawa","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.2353\/ajpath.2009.090318","article-title":"Epithelial Mesenchymal Transition in Human Ocular Chronic Graft-Versus-Host Disease","volume":"175","author":"Ogawa","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.jtos.2017.03.006","article-title":"TFOS DEWS II Tear Film Report","volume":"15","author":"Willcox","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_25","first-page":"797","article-title":"Cytokines in tear fluid of patients with ocular graft-versus-host disease after allogeneic stem cell transplantation","volume":"18","author":"Riemens","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1016\/j.bbmt.2015.08.020","article-title":"Tear Cytokines as Biomarkers for Chronic Graft-versus-Host Disease","volume":"21","author":"Jung","year":"2015","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jtos.2018.12.007","article-title":"Marked infiltration of neutrophils at the upper palpebral conjunctiva in patients with chronic graft-versus-host disease","volume":"17","author":"Byun","year":"2019","journal-title":"Ocul. Surf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jtos.2019.12.005","article-title":"Tear cytokine levels in the diagnosis and severity assessment of ocular chronic graft-versus-host disease(GVHD)","volume":"18","author":"Hu","year":"2020","journal-title":"Ocul. Surf."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1089\/jop.2015.0048","article-title":"Semifluorinated Alkane Eye Drops for Treatment of Dry Eye Disease--A Prospective, Multicenter Noninterventional Study","volume":"31","author":"Steven","year":"2015","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1167\/iovs.13-13265","article-title":"Significance of Ectodomain Shedding of TNF Receptor 1 in Ocular Surface","volume":"55","author":"Sakimoto","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8253","DOI":"10.1167\/iovs.12-10430","article-title":"Ocular Surface Extracellular DNA and Nuclease Activity Imbalance: A New Paradigm for Inflammation in Dry Eye Disease","volume":"53","author":"Sonawane","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jtos.2019.10.004","article-title":"Pathological consequences of anti-citrullinated protein antibodies in tear fluid and therapeutic potential of pooled human immune globulin-eye drops in dry eye disease","volume":"18","author":"Kwon","year":"2020","journal-title":"Ocul. Surf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ajo.2016.12.026","article-title":"Elevated Neutrophil Elastase in Tears of Ocular Graft-Versus-Host Disease Patients","volume":"176","author":"Arafat","year":"2017","journal-title":"Am. J. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1167\/iovs.15-18615","article-title":"Biomarkers in Ocular Chronic Graft Versus Host Disease: Tear Cytokine- and Chemokine-Based Predictive Model","volume":"57","author":"Cocho","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1167\/iovs.18-24433","article-title":"Tear Film Proteomics Reveal Important Differences Between Patients With and Without Ocular GvHD After Allogeneic Hematopoietic Cell Transplantation","volume":"59","author":"Plattner","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jtos.2018.11.001","article-title":"A novel and innovative paper-based analytical device for assessing tear lactoferrin of dry eye patients","volume":"17","author":"Sonobe","year":"2019","journal-title":"Ocul. Surf."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jtos.2019.02.001","article-title":"Commensal microflora in human conjunctiva; characteristics of microflora in the patients with chronic ocular graft-versus-host disease","volume":"17","author":"Shimizu","year":"2019","journal-title":"Ocul. Surf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1097\/ACI.0b013e3283303e1b","article-title":"The role of microbial flora on the ocular surface","volume":"9","author":"Miller","year":"2009","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"23561","DOI":"10.1038\/srep23561","article-title":"Altered Mucosal Microbiome Diversity and Disease Severity in Sj\u00f6gren Syndrome","volume":"6","author":"Jones","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-60794-w","article-title":"Comparison of the ocular microbiome between chronic Stevens-Johnson syndrome patients and healthy subjects","volume":"10","author":"Kittipibul","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.jtos.2020.07.007","article-title":"Assessing the ocular surface microbiome in severe ocular surface diseases","volume":"18","author":"Zilliox","year":"2020","journal-title":"Ocul. Surf."},{"key":"ref_42","first-page":"2533","article-title":"Morphologic evaluation of meibomian glands in chronic graft-versus-host disease using in vivo laser confocal microscopy","volume":"17","author":"Ban","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/02713683.2020.1846754","article-title":"The Association between Meibomian Gland Atrophy and Corneal Subbasal Nerve Loss in Patients with Chronic Ocular Graft-versus-host Disease","volume":"46","author":"Dikmetas","year":"2021","journal-title":"Curr. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/bmt.2015.72","article-title":"Meibography and meibomian gland measurements in ocular graft-versus-host disease","volume":"50","author":"Engel","year":"2015","journal-title":"Bone Marrow Transplant."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/ICO.0000000000001487","article-title":"Ocular Surface and Tear Film Characteristics in a Sclerodermatous Chronic Graft-Versus-Host Disease Mouse Model","volume":"37","author":"He","year":"2018","journal-title":"Cornea"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.jtos.2019.04.009","article-title":"Longitudinal analysis of meibomian gland dropout in patients with ocular graft-versus-host disease","volume":"17","author":"Hwang","year":"2019","journal-title":"Ocul. Surf."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.exer.2017.07.013","article-title":"Changes of meibomian glands in the early stage of post hematopoietic stem cell transplantation","volume":"163","author":"Kim","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1167\/iovs.02-0699","article-title":"Periductal Area as the Primary Site for T-Cell Activation in Lacrimal Gland Chronic Graft-Versus-Host Disease","volume":"44","author":"Ogawa","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/bmt.2011.89","article-title":"Mucosal microvilli in dry eye patients with chronic GVHD","volume":"47","author":"Tatematsu","year":"2012","journal-title":"Bone Marrow Transplant."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/sj.bmt.1705900","article-title":"Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease","volume":"41","author":"Wang","year":"2008","journal-title":"Bone Marrow Transplant."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1182\/blood.2019000823","article-title":"The primacy of gastrointestinal tract antigen-presenting cells in lethal graft-versus-host disease","volume":"134","author":"Koyama","year":"2019","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1056\/NEJMra1609337","article-title":"Acute Graft-versus-Host Disease\u2014Biologic Process, Prevention, and Therapy","volume":"377","author":"Zeiser","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1001\/archopht.1989.01070020413046","article-title":"The eye in bone marrow transplantation. III. Conjunctival graft-vs-host disease","volume":"107","author":"Jabs","year":"1989","journal-title":"Arch. Ophthalmol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1007\/BF02982052","article-title":"Ocular manifestation of acute graft-versus-host disease after allogeneic peripheral blood stem cell transplantation","volume":"75","author":"Saito","year":"2002","journal-title":"Int. J. Hematol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/j.1600-0420.2006.00658.x","article-title":"Ocular complications in a child with acute graft-versus-host disease following cord blood stem cell transplantation: Therapeutic challenges","volume":"84","author":"Uchino","year":"2006","journal-title":"Acta Ophthalmol. Scand"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hayashi, S., Shimizu, E., Uchino, M., Yazu, H., Aketa, N., Tsubota, K., and Ogawa, Y. (2020). The Overlap Syndrome: A Case Report of Chronic Graft-Versus-Host Disease After the Development of a Pseudomembrane. Cornea, online ahead of print.","DOI":"10.1097\/ICO.0000000000002593"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1097\/ICO.0b013e31820ce6d0","article-title":"Visual Acuity and Anterior Segment Findings in Chronic Graft-Versus-Host Disease","volume":"30","author":"Allan","year":"2011","journal-title":"Cornea"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1001\/archopht.1983.01040010580010","article-title":"The eye in bone marrow transplantation. I. Clinical study","volume":"101","author":"Hirst","year":"1983","journal-title":"Arch. Ophthalmol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1016\/S0161-6420(99)00720-4","article-title":"Ocular findings in allogeneic stem cell transplantation without total body irradiation","volume":"106","author":"Kerty","year":"1999","journal-title":"Ophthalmology"},{"key":"ref_60","first-page":"S177","article-title":"Ocular Graft vs. Host Disease","volume":"3","author":"Kim","year":"2005","journal-title":"Ocul. Surf."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"582098","DOI":"10.3389\/fimmu.2020.582098","article-title":"Helper Innate Lymphoid Cells in Allogenic Hematopoietic Stem Cell Transplantation and Graft Versus Host Disease","volume":"11","author":"Quatrini","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Shao, L., Pan, S., Zhang, Q.-P., Jamal, M., Chen, L.-H., Yin, Q., Wu, Y.-J., Xiong, J., Xiao, R.-J., and Kwong, Y.-L. (2019). An Essential Role of Innate Lymphoid Cells in the Pathophysiology of Graft-vs.-Host Disease. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01233"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3389\/fimmu.2016.00188","article-title":"NK Cells and Other Innate Lymphoid Cells in Hematopoietic Stem Cell Transplantation","volume":"7","author":"Vacca","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1111\/ajt.13394","article-title":"Innate lymphoid cells in graft-versus-host disease","volume":"15","author":"Konya","year":"2015","journal-title":"Am. J. Transplant."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1182\/blood-2013-11-536888","article-title":"Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease","volume":"124","author":"Munneke","year":"2014","journal-title":"Blood"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1167\/iovs.14-15630","article-title":"Recruitment of Donor T Cells to the Eyes During Ocular GVHD in Recipients of MHC-Matched Allogeneic Hematopoietic Stem Cell Transplants","volume":"56","author":"Herretes","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.1167\/iovs.05-0227","article-title":"Donor Fibroblast Chimerism in the Pathogenic Fibrotic Lesion of Human Chronic Graft-Versus-Host Disease","volume":"46","author":"Ogawa","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.exer.2005.02.004","article-title":"Cell populations and adhesion molecules expression in conjunctiva before and after bone marrow transplantation","volume":"81","author":"Rojas","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e09394","DOI":"10.7554\/eLife.09394","article-title":"MHC-compatible bone marrow stromal\/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model","volume":"5","author":"Ogawa","year":"2016","journal-title":"eLife"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.bbmt.2016.07.012","article-title":"Novel Scoring Criteria for the Evaluation of Ocular Graft-versus-Host Disease in a Preclinical Allogeneic Hematopoietic Stem Cell Transplantation Animal Model","volume":"22","author":"Perez","year":"2016","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_71","first-page":"1","article-title":"In Vivo Confocal Microscopy Evaluation of Ocular Surface with Graft-Versus-Host Disease-Related Dry Eye Disease","volume":"7","author":"He","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4686","DOI":"10.1167\/iovs.16-20013","article-title":"In Vivo Confocal Microscopy in Dry Eye Disease Associated With Chronic Graft-Versus-Host Disease","volume":"57","author":"Kheirkhah","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_73","first-page":"2605","article-title":"Toll-like receptor 2-mediated NF-\u03baB inflammatory responses in dry eye associated with cGVHD","volume":"17","author":"He","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/ni0407-345","article-title":"T(H)-17 cells in the circle of immunity and autoimmunity","volume":"8","author":"Bettelli","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1001\/archophthalmol.2011.364","article-title":"Dry eye disease: An immune-mediated ocular surface disorder","volume":"130","author":"Stevenson","year":"2012","journal-title":"Arch. Ophthalmol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/mi.2013.20","article-title":"Chronic dry eye disease is principally mediated by effector memory Th17 cells","volume":"7","author":"Chen","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3109\/08830185.2012.748052","article-title":"Dry Eye as a Mucosal Autoimmune Disease","volume":"32","author":"Stern","year":"2013","journal-title":"Int. Rev. Immunol."},{"key":"ref_78","first-page":"598","article-title":"Four cases of corneal perforation in patients with chronic graft-versus-host disease","volume":"17","author":"Inagaki","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/sj.eye.6702420","article-title":"A case of sterile corneal perforation after bone marrow transplantation","volume":"21","author":"Suzuki","year":"2007","journal-title":"Eye"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s00109-011-0767-x","article-title":"Danger signals activating innate immunity in graft-versus-host disease","volume":"89","author":"Zeiser","year":"2011","journal-title":"J. Mol. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.jtos.2019.03.010","article-title":"Neutrophil extracellular traps (NETs) contribute to pathological changes of ocular graft-vs.-host disease (oGVHD) dry eye: Implications for novel biomarkers and therapeutic strategies","volume":"17","author":"An","year":"2019","journal-title":"Ocul. Surf."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"8051","DOI":"10.1167\/iovs.13-12844","article-title":"Tear Fluid Extracellular DNA: Diagnostic and Therapeutic Implications in Dry Eye Disease","volume":"54","author":"Tibrewal","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"10778","DOI":"10.1096\/fj.201900218R","article-title":"Senescence-associated secretory phenotype promotes chronic ocular graft-vs-host disease in mice and humans","volume":"34","author":"Yamane","year":"2020","journal-title":"FASEB J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.3389\/fimmu.2020.01142","article-title":"T Cells in Fibrosis and Fibrotic Diseases","volume":"11","author":"Zhang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1167\/iovs.06-0601","article-title":"Role of Heat Shock Protein 47, a Collagen-Binding Chaperone, in Lacrimal Gland Pathology in Patients with cGVHD","volume":"48","author":"Ogawa","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1167\/iovs.02-1084","article-title":"Effects of IL-4 on Conjunctival Fibroblasts: Possible Role in Ocular Cicatricial Pemphigoid","volume":"44","author":"Razzaque","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1167\/iovs.02-0967","article-title":"Role of connective tissue growth factor in the pathogenesis of conjunctival scarring in ocular cicatricial pemphigoid","volume":"44","author":"Razzaque","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1167\/iovs.02-0644","article-title":"Role of collagen-binding heat shock protein 47 and transforming growth factor-beta1 in conjunctival scarring in ocular cicatricial pemphigoid","volume":"44","author":"Razzaque","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1073\/pnas.94.12.6307","article-title":"The peripheral blood fibrocyte is a potent antigen-presenting cell capable of priming naive T cells in situ","volume":"94","author":"Chesney","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","first-page":"19","article-title":"Flow Cytometric Identification of Fibrocytes in the Human Circulation","volume":"1343","author":"Hu","year":"2015","journal-title":"Advanced Structural Safety Studies"},{"key":"ref_91","first-page":"309","article-title":"Ultrastructural and immunohistochemical observations on intralobular fibroblasts of human breast, with observations on the CD34 antigen","volume":"27","author":"Yamazaki","year":"1995","journal-title":"J. Submicrosc. Cytol. Pathol."},{"key":"ref_92","first-page":"471","article-title":"Ultrastructural and immunohistochemical studies of intralobular fibroblasts in human submandibular gland: The recognition of a \u2018CD34 positive reticular network\u2019 connected by gap junctions","volume":"28","author":"Yamazaki","year":"1996","journal-title":"J. Submicrosc. Cytol. Pathol."},{"key":"ref_93","first-page":"461","article-title":"Interfollicular fibroblasts in the human thyroid gland: Recognition of a CD34 positive stromal cell network communicated by gap junctions and terminated by autonomic nerve endings","volume":"29","author":"Yamazaki","year":"1997","journal-title":"J. Submicrosc. Cytol. Pathol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.stem.2013.09.006","article-title":"Mesenchymal Stromal Cells: Sensors and Switchers of Inflammation","volume":"13","author":"Bernardo","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.jtos.2019.01.001","article-title":"Subconjunctival injection of mesenchymal stromal cells protects the cornea in an experimental model of GVHD","volume":"17","author":"Velasco","year":"2019","journal-title":"Ocul. Surf."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.3727\/096368915X687480","article-title":"Human Bone Marrow Stromal Cells Differentiate into Corneal Tissue and Prevent Ocular Graft-Versus-Host Disease in Mice","volume":"24","author":"Lorenzo","year":"2015","journal-title":"Cell Transplant."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1167\/iovs.61.5.15","article-title":"KLF4 Coordinates Corneal Epithelial Apical-Basal Polarity and Plane of Cell Division and Is Downregulated in Ocular Surface Squamous Neoplasia","volume":"61","author":"Tiwari","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"108047","DOI":"10.1016\/j.exer.2020.108047","article-title":"DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells","volume":"197","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.reth.2019.06.005","article-title":"The secretome of adipose-derived mesenchymal stem cells attenuates epithelial\u2013mesenchymal transition in human corneal epithelium","volume":"11","author":"Shibata","year":"2019","journal-title":"Regen. Ther."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1167\/iovs.14-16300","article-title":"Merlin regulates the epithelial-to-mesenchymal transition of ARPE-19 cells via TAK1-p38MAPK-mediated activation","volume":"56","author":"Takahashi","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1172\/JCI200320530","article-title":"Epithelial-mesenchymal transition and its implications for fibrosis","volume":"112","author":"Kalluri","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.ygyno.2007.08.058","article-title":"Irradiation-induced epithelial\u2013mesenchymal transition (EMT) related to invasive potential in endometrial carcinoma cells","volume":"107","author":"Tsukamoto","year":"2007","journal-title":"Gynecol. Oncol."},{"key":"ref_103","first-page":"3810","article-title":"Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition","volume":"117","author":"Higgins","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_104","first-page":"123","article-title":"Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability","volume":"436","author":"Radisky","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41580-020-0237-9","article-title":"Guidelines and definitions for research on epithelial\u2013mesenchymal transition","volume":"21","author":"Yang","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1165\/rcmb.2007-0071OC","article-title":"Collagen I promotes epithelial-to-mesenchymal transition in lung cancer cells via transforming growth factor-beta signaling","volume":"38","author":"Shintani","year":"2008","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1038\/srep02455","article-title":"Expression and localization of aging markers in lacrimal gland of chronic graft-versus-host disease","volume":"3","author":"Kawai","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1172\/JCI122899","article-title":"Thioredoxin-1 confines T cell alloresponse and pathogenicity in graft-versus-host disease","volume":"129","author":"Sofi","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1089\/152308603770310202","article-title":"The Free Radical Theory of Aging","volume":"5","author":"Harman","year":"2003","journal-title":"Antioxidants Redox Signal."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Yaguchi, S., Ogawa, Y., Shimmura, S., Kawakita, T., Hatou, S., Satofuka, S., Nakamura, S., Imada, T., Miyashita, H., and Yoshida, S. (2013). Angiotensin II Type 1 Receptor Antagonist Attenuates Lacrimal Gland, Lung, and Liver Fibrosis in a Murine Model of Chronic Graft-Versus-Host Disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064724"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1096\/fj.201700176R","article-title":"Inhibition of Vascular Adhesion Protein-1 for Treatment of Graft-Versus-Host Disease in Mice","volume":"32","author":"Mukai","year":"2018","journal-title":"FASEB J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"41939","DOI":"10.1038\/srep41939","article-title":"Novel Treatment of Chronic Graft-Versus-Host Disease in Mice Using the ER Stress Reducer 4-Phenylbutyric Acid","volume":"7","author":"Mukai","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nature12347","article-title":"Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome","volume":"499","author":"Yoshimoto","year":"2013","journal-title":"Nature"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ebiom.2018.05.035","article-title":"Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging","volume":"32","author":"Lin","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"80208","DOI":"10.18632\/oncotarget.13303","article-title":"Mitochondria-targeted antioxidant SkQ1 reduces age-related alterations in the ultrastructure of the lacrimal gland","volume":"7","author":"Bakeeva","year":"2016","journal-title":"Oncotarget"},{"key":"ref_117","first-page":"194","article-title":"Age-dependent changes in rat lacrimal gland anti-oxidant and vesicular related protein expression profiles","volume":"18","author":"Batista","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Uchino, Y., Kawakita, T., Miyazawa, M., Ishii, T., Onouchi, H., Yasuda, K., Ogawa, Y., Shimmura, S., Ishii, N., and Tsubota, K. (2012). Oxidative Stress Induced Inflammation Initiates Functional Decline of Tear Production. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045805"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"DES163","DOI":"10.1167\/iovs.17-23402","article-title":"Potential Role of Oxidative Stress in Ocular Surface Inflammation and Dry Eye Disease","volume":"59","author":"Dogru","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3389\/fphys.2014.00439","article-title":"The impact of age-related dysregulation of the angiotensin system on mitochondrial redox balance","volume":"5","author":"Vajapey","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/emmm.201000080","article-title":"Angiotensin II revisited: New roles in inflammation, immunology and aging","volume":"2","author":"Benigni","year":"2010","journal-title":"EMBO Mol. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0140-6736(05)78218-0","article-title":"Accelerated telomere shortening in bone-marrow recipients","volume":"351","author":"Shay","year":"1998","journal-title":"Lancet"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.molmed.2012.06.010","article-title":"ER stress-induced inflammation: Does it aid or impede disease progression?","volume":"18","author":"Garg","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"84","DOI":"10.18632\/aging.100531","article-title":"The role of inflammation in age-related disease","volume":"5","author":"Howcroft","year":"2013","journal-title":"Aging"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.ymeth.2004.10.010","article-title":"The ER chaperone and signaling regulator GRP78\/BiP as a monitor of endoplasmic reticulum stress","volume":"35","author":"Lee","year":"2005","journal-title":"Methods"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1007\/s00125-015-3669-6","article-title":"Cytokines induce endoplasmic reticulum stress in human, rat and mouse beta cells via different mechanisms","volume":"58","author":"Brozzi","year":"2015","journal-title":"Diabetol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cmet.2012.07.012","article-title":"TXNIP Switches Tracks toward a Terminal UPR","volume":"16","author":"Anthony","year":"2012","journal-title":"Cell Metab."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1002\/eji.200838651","article-title":"Ischemia-reperfusion injury is attenuated in VAP-1-deficient mice and by VAP-1 inhibitors","volume":"38","author":"Kiss","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/nri1705","article-title":"Cell-surface enzymes in control of leukocyte trafficking","volume":"5","author":"Salmi","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1124\/jpet.113.207613","article-title":"PXS-4681A, a Potent and Selective Mechanism-Based Inhibitor of SSAO\/VAP-1 with Anti-Inflammatory Effects In Vivo","volume":"347","author":"Foot","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1182\/blood-2013-08-520072","article-title":"Plasma CXCL9 elevations correlate with chronic GVHD diagnosis","volume":"123","author":"Kitko","year":"2014","journal-title":"Blood"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1097\/ICU.0000000000000400","article-title":"Graft versus host disease: What should the oculoplastic surgeon know?","volume":"28","author":"Tung","year":"2017","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1097\/IIO.0000000000000167","article-title":"Current Approaches to Treatment of Ocular Graft-Versus-Host Disease","volume":"57","author":"Tung","year":"2017","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1007\/s00417-013-2301-z","article-title":"Graft versus host disease: Clinical evaluation, diagnosis and management","volume":"251","author":"Espana","year":"2013","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1097\/ICU.0b013e32833eab64","article-title":"Current insights into ocular graft-versus-host disease","volume":"21","author":"Riemens","year":"2010","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.4103\/ijo.IJO_2016_20","article-title":"Update on ocular graft-versus-host disease","volume":"69","author":"Vanathi","year":"2021","journal-title":"Indian J. Ophthalmol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1097\/ACI.0b013e328357b4b9","article-title":"Ocular graft-versus-host disease","volume":"12","author":"Hessen","year":"2012","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"S215","DOI":"10.1097\/ICL.0000000000000455","article-title":"Long-Term Topical Diquafosol Tetrasodium Treatment of Dry Eye Disease Caused by Chronic Graft-Versus-Host Disease: A Retrospective Study","volume":"44","author":"Yamane","year":"2018","journal-title":"Eye Contact Lens Sci. Clin. Pr."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/bmt.2011.205","article-title":"Punctal occlusion is safe and efficient for the treatment of keratoconjunctivitis sicca in patients with ocular GvHD","volume":"47","author":"Sabti","year":"2012","journal-title":"Bone Marrow Transpl."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1038\/bmt.2012.50","article-title":"Surgical management of lacrimal punctal cauterization in chronic GVHD-related dry eye with recurrent punctal plug extrusion","volume":"47","author":"Yaguchi","year":"2012","journal-title":"Bone Marrow Transplant."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/sj.bmt.1705621","article-title":"Effect of pilocarpine hydrochloride on unstimulated whole saliva flow rate and composition in patients with chronic graft-versus-host disease (cGVHD)","volume":"39","author":"Ghavamzadeh","year":"2007","journal-title":"Bone Marrow Transpl."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1097\/OPX.0000000000000523","article-title":"Long-term Rebamipide and Diquafosol in Two Cases of Immune-Mediated Dry Eye","volume":"92","author":"Yamane","year":"2015","journal-title":"Optom. Vis. Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1097\/ICO.0b013e318226bf97","article-title":"Diagnosis and treatment of ocular chronic graft-versus-host disease: Report from the German-Austrian-Swiss Consensus Conference on Clinical Practice in chronic GVHD","volume":"31","year":"2012","journal-title":"Cornea"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.ophtha.2016.02.044","article-title":"A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease","volume":"123","author":"Abud","year":"2016","journal-title":"Ophthalmol."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Sato, S., Shimizu, E., He, J., Ogawa, M., Asai, K., Yazu, H., Rusch, R., Yamane, M., Yang, F., and Fukuda, S. (2021). Positive Effects of Oral Antibiotic Administration in Murine Chronic Graft-Versus-Host Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073745"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.ajo.2014.11.035","article-title":"Long-term Result of Maintenance Treatment With Tacrolimus Ointment in Chronic Ocular Graft-Versus-Host Disease","volume":"159","author":"Jung","year":"2015","journal-title":"Am. J. Ophthalmol."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Poe, J.C., Jia, W., Di Paolo, J.A., Reyes, N.J., Kim, J.Y., Su, H., Sundy, J.S., Cardones, A.R., Perez, V.L., and Chen, B.J. (2018). SYK inhibitor entospletinib prevents ocular and skin GVHD in mice. JCI Insight, 3.","DOI":"10.1172\/jci.insight.122430"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/sj.bmt.1703862","article-title":"Autologous serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease","volume":"31","author":"Ogawa","year":"2003","journal-title":"Bone Marrow Transplant."},{"key":"ref_149","first-page":"322","article-title":"Treatment of severe chronic ocular graft-versus-host disease using 100% autologous serum eye drops from a sealed manufacturing system: A retrospective cohort study","volume":"101","author":"Tahmaz","year":"2017","journal-title":"Br. J. Ophthalmol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/sj.bmt.1705566","article-title":"Therapeutic effect of umbilical cord serum eyedrops for the treatment of dry eye associated with graft-versus-host disease","volume":"39","author":"Yoon","year":"2007","journal-title":"Bone Marrow Transplant."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jtos.2017.05.006","article-title":"TFOS DEWS II Management and Therapy Report","volume":"15","author":"Jones","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/bmt.2016.221","article-title":"Long-term safety and efficacy of autologous platelet lysate drops for treatment of ocular GvHD","volume":"52","author":"Pezzotta","year":"2017","journal-title":"Bone Marrow Transplant."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/vox.12325","article-title":"Cytokine profile of autologous platelet-derived eye drops in patients with ocular chronic graft-versus-host disease","volume":"110","author":"Valentini","year":"2016","journal-title":"Vox Sang."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12886-021-01925-3","article-title":"Two case reports of continued progression of chronic ocular graft-versus-host disease without concurrent systemic comorbidities treated by amniotic membrane transplantation","volume":"21","author":"Ikarashi","year":"2021","journal-title":"BMC Ophthalmol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jtos.2015.07.002","article-title":"A Novel Technique for Amniotic Membrane Transplantation in Patients with Acute Stevens-Johnson Syndrome","volume":"14","author":"Ma","year":"2016","journal-title":"Ocul. Surf."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"108","DOI":"10.4103\/2008-322X.180705","article-title":"Recurrent Corneal Perforation due to Chronic Graft versus Host Disease; a Clinicopathologic Report","volume":"11","author":"Mohammadpour","year":"2016","journal-title":"J. Ophthalmic Vis. Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/S0929-6646(09)60125-X","article-title":"Recurrent Corneal Perforation and Acute Calcareous Corneal Degeneration in Chronic Graft-Versus-Host Disease","volume":"105","author":"Yen","year":"2006","journal-title":"J. Formos. Med Assoc."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/ICO.0b013e31818526a6","article-title":"Ocular Surface Reconstruction in Graft-Versus-Host Disease With HLA-Identical Living-Related Allogeneic Cultivated Limbal Epithelium After Hematopoietic Stem Cell Transplantation from the Same Donor","volume":"28","author":"Meller","year":"2009","journal-title":"Cornea"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1097\/ICL.0000000000000186","article-title":"PROSE Treatment for Ocular Chronic Graft-Versus-Host Disease as a Clinical Network Expands","volume":"42","author":"DeLoss","year":"2016","journal-title":"Eye Contact Lens: Sci. Clin. Pr."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1016\/j.bbmt.2015.07.013","article-title":"Bandage Soft Contact Lenses for Ocular Graft-versus-Host Disease","volume":"21","author":"Inamoto","year":"2015","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/01.icl.0000244154.76214.2d","article-title":"Extended-Wear Silicone Hydrogel Soft Contact Lenses in the Management of Moderate to Severe Dry Eye Signs and Symptoms Secondary to Graft-Versus-Host Disease","volume":"33","author":"Russo","year":"2007","journal-title":"Eye Contact Lens Sci. Clin. Pr."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1182\/bloodadvances.2018028431","article-title":"Ocular instillation of vitamin A\u2013coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic GVHD","volume":"3","author":"Ohigashi","year":"2019","journal-title":"Blood Adv."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1038\/s41409-020-0824-6","article-title":"Adverse environmental conditions are a risk factor for ocular GvHD after allogeneic hematopoietic stem cell transplantation","volume":"55","author":"Steven","year":"2020","journal-title":"Bone Marrow Transplant."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1097\/IOP.0000000000000592","article-title":"A Case of a Bilateral Cicatricial Upper Eyelid Entropion After Hematopoietic Stem Cell Transplantation in Mucopolysaccharidosis Type I","volume":"33","author":"Dulz","year":"2017","journal-title":"Ophthalmic Plast. Reconstr. Surg."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S0002-9394(14)71750-7","article-title":"Efficacy of Doxycycline and Tetracycline in Ocular Rosacea","volume":"116","author":"Sagi","year":"1993","journal-title":"Am. J. Ophthalmol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/sj.bmt.1704453","article-title":"Topical corticosteroid therapy for cicatricial conjunctivitis associated with chronic graft-versus-host disease","volume":"33","author":"Robinson","year":"2004","journal-title":"Bone Marrow Transplant."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1089\/jop.2018.0006","article-title":"Topical Cyclosporine Pretreatment of Ocular Surface in Allogeneic Hematopoietic Stem Cell Transplant Recipients","volume":"34","author":"Chun","year":"2018","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ajo.2018.03.024","article-title":"Reduced Efficacy of Low-dose Topical Steroids in Dry Eye Disease Associated With Graft-versus-Host Disease","volume":"190","author":"Yin","year":"2018","journal-title":"Am. J. Ophthalmol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1080\/10428194.2019.1695049","article-title":"Lifitegrast ophthalmic solution for treatment of ocular chronic graft-versus-host disease","volume":"61","author":"Chhabra","year":"2019","journal-title":"Leuk. Lymphoma"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.jfo.2020.12.004","article-title":"Eye amputation following lifitegrast treatment for ocular graft-versus-host disease: First case report","volume":"44","author":"Ferrete","year":"2021","journal-title":"J. Fr. d\u2019Ophtalmol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1001\/jamaophthalmol.2013.195","article-title":"Topical interleukin 1 receptor antagonist for treatment of dry eye disease: A randomized clinical trial","volume":"131","author":"Amparo","year":"2013","journal-title":"JAMA Ophthalmol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.phrs.2014.10.009","article-title":"Tranilast: A review of its therapeutic applications","volume":"91","author":"Darakhshan","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.bcp.2011.06.013","article-title":"Suppression of human CD4+ T cell activation by 3,4-dimethoxycinnamonyl-anthranilic acid (tranilast) is mediated by CXCL9 and CXCL10","volume":"82","author":"Hertenstein","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/bmt.2009.173","article-title":"Topical tranilast for treatment of the early stage of mild dry eye associated with chronic GVHD","volume":"45","author":"Ogawa","year":"2010","journal-title":"Bone Marrow Transplant."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/sj.bmt.1702334","article-title":"GVHD dry eyes treated with autologous serum tears","volume":"25","author":"Rocha","year":"2000","journal-title":"Bone Marrow Transplant."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1097\/ICO.0b013e3180645cd7","article-title":"Allogeneic Serum Eye Drops for the Treatment of Severe Dry Eye in Patients With Chronic Graft-Versus-Host Disease","volume":"26","author":"Chiang","year":"2007","journal-title":"Cornea"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00417-020-04865-8","article-title":"Detection of systemic immunosuppressants in autologous serum eye drops (ASED) in patients with severe chronic ocular graft versus host disease","volume":"259","author":"Tahmaz","year":"2021","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1182\/blood-2008-03-141481","article-title":"A multicenter prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease","volume":"112","author":"Flowers","year":"2008","journal-title":"Blood"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1111\/j.1537-2995.2009.02577.x","article-title":"Extracorporeal photochemotherapy in graft-versus-host disease: A longitudinal study on factors influencing the response and survival in pediatric patients","volume":"50","author":"Perotti","year":"2010","journal-title":"Transfus."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.jtos.2018.04.007","article-title":"Tear inflammatory mediators and protein in eyes of post allogenic hematopoeitic stem cell transplant patients","volume":"16","author":"Nair","year":"2018","journal-title":"Ocul. Surf."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"4570","DOI":"10.1167\/iovs.15-16736","article-title":"Gene Expression\u2013Based Predictive Models of Graft Versus Host Disease\u2013Associated Dry Eye","volume":"56","author":"Cocho","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1080\/10428194.2019.1573996","article-title":"Tocilizumab as first-line therapy for steroid-refractory acute graft-versus-host-disease: Analysis of a single-center experience","volume":"60","author":"Yucebay","year":"2019","journal-title":"Leuk. lymphoma"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s00277-020-03968-w","article-title":"IL6-receptor antibody tocilizumab as salvage therapy in severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: A retrospective analysis","volume":"99","author":"Kattner","year":"2020","journal-title":"Ann. Hematol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/annrheumdis-2019-216655","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update","volume":"79","author":"Smolen","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1097\/ICO.0000000000001206","article-title":"A Pilot Randomized Trial on Safety and Efficacy of a Novel Topical Combined Inhibitor of Janus Kinase 1\/3 and Spleen Tyrosine Kinase for GVHD-Associated Ocular Surface Disease","volume":"36","author":"Kheirkhah","year":"2017","journal-title":"Cornea"},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Mukai, S., Ogawa, Y., Saya, H., Kawakami, Y., and Tsubota, K. (2018). Therapeutic potential of tranilast for the treatment of chronic graft-versus-host disease in mice. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0203742"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"42195","DOI":"10.1038\/srep42195","article-title":"Heavy Chain-Hyaluronan\/Pentraxin 3 from Amniotic Membrane Suppresses Inflammation and Scarring in Murine Lacrimal Gland and Conjunctiva of Chronic Graft-versus-Host Disease","volume":"7","author":"Ogawa","year":"2017","journal-title":"Sci. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6114\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:11:25Z","timestamp":1760163085000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,6]]},"references-count":187,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22116114"],"URL":"https:\/\/doi.org\/10.3390\/ijms22116114","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,6]]}}}