{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:46:52Z","timestamp":1792615612439,"version":"4.5.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"publisher","award":["EY005093"],"award-info":[{"award-number":["EY005093"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["EY023027"],"award-info":[{"award-number":["EY023027"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Stromal keratitis (SK) is a chronic immunopathological lesion of the eye, caused by HSV-1 infection, and a common cause of vision impairment in humans. The inflammatory lesions in the cornea are primarily caused by neutrophils with the active participation of CD4+ T cells. Therefore, the targeting of these immune cell types and their products represents a potentially valuable form of therapy to reduce the severity of disease. Resolvin D1 (RvD1) and its epimer aspirin-triggered RvD1 (AT-RvD1) are lipid mediators derived from docosahexaenoic acid (DHA) and were shown to promote resolution in several inflammatory disease models. In this report, we examined whether AT-RvD1 administration, begun before infection or at a later stage after ocular infection of mice with HSV-1, could control the severity of SK lesions. Treatment with AT-RvD1 significantly diminished the extent of corneal neovascularization and the severity of SK lesions. AT-RvD1-treated mice had fewer numbers of inflammatory cells that included neutrophils as well as Th1 and Th17 cells in the infected cornea. The mechanisms by which AT-RvD1 acts appear to be multiple. These include inhibitory effects on proinflammatory mediators, such as IL-1\u03b2, IL-6, IL-12, CXCL1, MCP-1, MIP-2, vascular endothelial growth factor (VEGF)-A, matrix metalloproteinase 9 (MMP-9), and proinflammatory miRNA, such as miR-155, miR-132, and miR-223, which are involved in SK pathogenesis and corneal neovascularization. In addition, AT-RvD1 attenuated STAT1, which plays an important role in Th1 cell differentiation and IFN-\u03b3 expression. These findings demonstrate that AT-RvD1 treatment could represent a useful strategy for the management of virus-induced immunopathological lesions.<\/jats:p>","DOI":"10.1189\/jlb.3hi1216-511rr","type":"journal-article","created":{"date-parts":[[2017,6,6]],"date-time":"2017-06-06T00:40:28Z","timestamp":1496709628000},"page":"1159-1171","source":"Crossref","is-referenced-by-count":56,"title":["Frontline Science: Aspirin-triggered resolvin D1 controls herpes simplex virus-induced corneal immunopathology"],"prefix":"10.1093","volume":"102","author":[{"given":"Naveen K","family":"Rajasagi","sequence":"first","affiliation":[{"name":"Biomedical and Diagnostic Sciences, College of Veterinary Medicine, The University of Tennessee , Knoxville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddheshvar","family":"Bhela","sequence":"additional","affiliation":[{"name":"Biomedical and Diagnostic Sciences, College of Veterinary Medicine, The University of Tennessee , Knoxville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siva Karthik","family":"Varanasi","sequence":"additional","affiliation":[{"name":"Department of Genome Science and Technology, The University of Tennessee , Knoxville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry T","family":"Rouse","sequence":"additional","affiliation":[{"name":"Biomedical and Diagnostic Sciences, College of Veterinary Medicine, The University of Tennessee , Knoxville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,11,1]]},"reference":[{"key":"2023013012234653300_B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00003226-200101000-00001","article-title":"Herpes simplex virus epidemiology and ocular importance","volume":"20","author":"Liesegang","year":"2001","journal-title":"Cornea"},{"key":"2023013012234653300_B2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.preteyeres.2012.08.002","article-title":"Herpes keratitis","volume":"32","author":"Rowe","year":"2013","journal-title":"Prog. 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