{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:42:51Z","timestamp":1788385371810,"version":"build-2803163510"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2017,1,23]],"date-time":"2017-01-23T00:00:00Z","timestamp":1485129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"publisher","award":["R01 EY021238"],"award-info":[{"award-number":["R01 EY021238"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["NEI core P30 EY021725"],"award-info":[{"award-number":["NEI core P30 EY021725"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Oklahoma Center for Adult Stem Cell Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Herpes simplex virus type 1 (HSV-1) is a leading cause of neurotrophic keratitis (NTK). NTK is characterized by decreased corneal sensation from damage to the corneal sensory fibers. We have reported on the regression of corneal nerves and their function during acute HSV-1 infection. That nerve loss is followed by an aberrant process of nerve regeneration during the latent phase of infection that lacks functional recovery. We recently showed the elicited immune response in the infected cornea, and not viral replication itself, is part of the mechanism responsible for the nerve degeneration process after infection. Specifically, we showed infected corneas topically treated with dexamethasone (DEX) significantly retained both structure and sensitivity of the corneal nerve network in comparison to mice treated with control eye drops, consistent with decreased levels of proinflammatory cytokines and reduced influx of macrophages and CD8+ T cells into the cornea. This study was undertaken to analyze the long-term effect of such a localized, immunosuppressive paradigm (DEX drops on the cornea surface during the first 8 d of HSV-1 infection) on the immune system and on corneal pathology. We found the profound immunosuppressive effect of DEX on lymphoid tissue was sustained in surviving mice for up to 30 d postinfection (p.i.). DEX treatment had prolonged effects, preserving corneal innervation and its function and blunting neovascularization, as analyzed at 30 d p.i. Our data support previously reported observations of an association between the persistent presence of inflammatory components in the latently infected cornea and structural and functional nerve defects in NTK.<\/jats:p>","DOI":"10.1189\/jlb.4a1116-459r","type":"journal-article","created":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T02:50:25Z","timestamp":1485226225000},"page":"1253-1261","source":"Crossref","is-referenced-by-count":9,"title":["Long-term consequences of topical dexamethasone treatment during acute corneal HSV-1 infection on the immune system"],"prefix":"10.1093","volume":"101","author":[{"given":"Ana J","family":"Chucair-Elliott","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan M","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J J","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA"},{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,1,23]]},"reference":[{"key":"2023011712222368000_B1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0014-4835(03)00050-2","article-title":"Corneal nerves: structure, contents and function","volume":"76","author":"M\u00fcller","year":"2003","journal-title":"Exp. Eye Res."},{"key":"2023011712222368000_B2","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/0014-4886(80)90154-5","article-title":"Sensory denervation of the rabbit cornea affects epithelial properties","volume":"69","author":"Beuerman","year":"1980","journal-title":"Exp. Neurol."},{"key":"2023011712222368000_B3","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1038\/sj.eye.6700616","article-title":"Neurotrophic keratitis","volume":"17","author":"Bonini","year":"2003","journal-title":"Eye (Lond.)"},{"key":"2023011712222368000_B4","first-page":"571","article-title":"Diagnosis and management of neurotrophic keratitis","volume":"8","author":"Sacchetti","year":"2014","journal-title":"Clin. Ophthalmol."},{"key":"2023011712222368000_B5","first-page":"754","article-title":"The pathogenesis and treatment of persistent epithelial defects","volume":"81","author":"Cavanagh","year":"1976","journal-title":"Trans. Sect. Ophthalmol. Am. Acad. Ophthalmol. Otolaryngol."},{"key":"2023011712222368000_B6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00004397-200101000-00003","article-title":"Neurotrophic keratitis","volume":"41","author":"Davis","year":"2001","journal-title":"Int. Ophthalmol. Clin."},{"key":"2023011712222368000_B7","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/S0161-6420(85)34034-4","article-title":"Corneal complications from herpes zoster ophthalmicus","volume":"92","author":"Liesegang","year":"1985","journal-title":"Ophthalmology"},{"key":"2023011712222368000_B8","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1177\/10454411980090040901","article-title":"Molecular aspects of herpes simplex virus I latency, reactivation, and recurrence","volume":"9","author":"Miller","year":"1998","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"2023011712222368000_B9","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.micinf.2005.03.003","article-title":"Early events in HSV keratitis setting the stage for a blinding disease","volume":"7","author":"Biswas","year":"2005","journal-title":"Microbes Infect."},{"key":"2023011712222368000_B10","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1177\/153537020122600501","article-title":"The immune response to ocular herpes simplex virus type 1 infection","volume":"226","author":"Carr","year":"2001","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"2023011712222368000_B11","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. Retin. Eye Res."},{"key":"2023011712222368000_B12","first-page":"372","article-title":"Cytokine production in a murine model of recurrent herpetic stromal keratitis","volume":"42","author":"Stumpf","year":"2001","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023011712222368000_B13","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1084\/jem.20091385","article-title":"VEGF-A expression by HSV-1-infected cells drives corneal lymphangiogenesis","volume":"207","author":"Wuest","year":"2010","journal-title":"J. Exp. Med."},{"key":"2023011712222368000_B14","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/S0002-9440(10)61777-4","article-title":"Control of stromal keratitis by inhibition of neovascularization","volume":"159","author":"Zheng","year":"2001","journal-title":"Am. J. Pathol."},{"key":"2023011712222368000_B15","doi-asserted-by":"crossref","first-page":"4516","DOI":"10.1167\/iovs.10-5225","article-title":"Selective changes in human corneal sensation associated with herpes simplex virus keratitis","volume":"51","author":"Gallar","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023011712222368000_B16","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1016\/j.ophtha.2010.07.010","article-title":"Corneal sensation and subbasal nerve alterations in patients with herpes simplex keratitis: an in vivo confocal microscopy study","volume":"117","author":"Hamrah","year":"2010","journal-title":"Ophthalmology"},{"key":"2023011712222368000_B17","doi-asserted-by":"crossref","first-page":"7870","DOI":"10.1128\/JVI.01146-14","article-title":"Reversible nerve damage and corneal pathology in murine herpes simplex stromal keratitis","volume":"88","author":"Yun","year":"2014","journal-title":"J. Virol."},{"key":"2023011712222368000_B18","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1167\/iovs.14-15596","article-title":"Degeneration and regeneration of corneal nerves in response to HSV-1 infection","volume":"56","author":"Chucair-Elliott","year":"2015","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023011712222368000_B19","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1167\/iovs.16-19183","article-title":"A central role for sympathetic nerves in herpes stromal keratitis in mice","volume":"57","author":"Yun","year":"2016","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023011712222368000_B20","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.exer.2014.06.006","article-title":"Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model","volume":"125","author":"Mirabelli","year":"2014","journal-title":"Exp. Eye Res."},{"key":"2023011712222368000_B21","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1016\/S0161-6420(02)01176-4","article-title":"Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate","volume":"109","author":"Weijtens","year":"2002","journal-title":"Ophthalmology"},{"key":"2023011712222368000_B22","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1016\/j.ajpath.2016.06.007","article-title":"IL-6 contributes to corneal nerve degeneration after herpes simplex virus type I infection","volume":"186","author":"Chucair-Elliott","year":"2016","journal-title":"Am. J. Pathol."},{"key":"2023011712222368000_B23","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.4049\/jimmunol.1600207","article-title":"Resident T cells are unable to control herpes simplex virus-1 activity in the brain ependymal region during latency","volume":"197","author":"Menendez","year":"2016","journal-title":"J. Immunol."},{"key":"2023011712222368000_B24","doi-asserted-by":"crossref","first-page":"5514","DOI":"10.1128\/JVI.00517-16","article-title":"A highly efficacious herpes simplex virus 1 vaccine blocks viral pathogenesis and prevents corneal immunopathology via humoral immunity","volume":"90","author":"Royer","year":"2016","journal-title":"J. Virol."},{"key":"2023011712222368000_B25","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.preteyeres.2006.05.001","article-title":"Herpes simplex keratitis","volume":"25","author":"Kaye","year":"2006","journal-title":"Prog. Retin. Eye Res."},{"key":"2023011712222368000_B26","doi-asserted-by":"crossref","first-page":"870","DOI":"10.3109\/02713683.2014.964419","article-title":"Dexamethasone\/povidone eye drops versus artificial tears for treatment of presumed viral conjunctivitis: a randomized clinical trial","volume":"40","author":"Pinto","year":"2014","journal-title":"Curr. Eye Res."},{"key":"2023011712222368000_B27","first-page":"1558","article-title":"Ocular herpes simplex virus reactivation in mice latently infected with latency-associated transcript mutants","volume":"32","author":"Cook","year":"1991","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023011712222368000_B28","doi-asserted-by":"crossref","first-page":"5051","DOI":"10.1128\/jvi.70.8.5051-5060.1996","article-title":"Mechanisms of herpes simplex virus type 1 reactivation","volume":"70","author":"Halford","year":"1996","journal-title":"J. Virol."},{"key":"2023011712222368000_B29","first-page":"371","article-title":"Recurrent HSV-1 corneal lesions in rabbits induced by cyclophosphamide and dexamethasone","volume":"30","author":"Haruta","year":"1989","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023011712222368000_B30","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1099\/0022-1317-71-2-397","article-title":"Reactivation of latent infection and induction of recurrent herpetic eye disease in mice","volume":"71","author":"Shimeld","year":"1990","journal-title":"J. Gen. Virol."},{"key":"2023011712222368000_B31","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1016\/S0161-6420(13)31155-5","article-title":"Herpetic eye disease study: a controlled trial of oral acyclovir for herpes simplex stromal keratitis","volume":"101","author":"Barron","year":"1994","journal-title":"Ophthalmology"},{"key":"2023011712222368000_B32","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1016\/S0161-6420(94)31087-6","article-title":"Herpetic eye disease study: a controlled trial of topical corticosteroids for herpes simplex stromal keratitis","volume":"101","author":"Wilhelmus","year":"1994","journal-title":"Ophthalmology"},{"key":"2023011712222368000_B33","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.4049\/jimmunol.1203265","article-title":"Microglia and a functional type I IFN pathway are required to counter HSV-1-driven brain lateral ventricle enlargement and encephalitis","volume":"190","author":"Conrady","year":"2013","journal-title":"J. Immunol."},{"key":"2023011712222368000_B34","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.4049\/jimmunol.1600574","article-title":"Herpesvirus-associated lymphadenitis distorts fibroblastic reticular cell microarchitecture and attenuates CD8 T cell responses to neurotropic infection in mice lacking the STING-IFN\u03b1\/\u03b2 defense pathways","volume":"197","author":"Royer","year":"2016","journal-title":"J. Immunol."}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/101\/5\/1253\/48718957\/jlb1253.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/101\/5\/1253\/48718957\/jlb1253.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T13:35:48Z","timestamp":1677504948000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/101\/5\/1253\/6933074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,23]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,1,23]]},"published-print":{"date-parts":[[2017,5,1]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.4a1116-459r","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,5]]},"published":{"date-parts":[[2017,1,23]]}}}