title: Enhanced cytomegalovirus infection in human trabecular meshwork cells and its implication in glaucoma pathogenesis.
abstract: Cytomegalovirus (CMV) is one of the infectious causes of hypertensive anterior uveitis, which is characterized by recurrent episodes of elevated intraocular pressure (IOP) and mild anterior uveitis. Despite the potentially vision-threatening complications of this disease, the underlying mechanisms remain largely undefined. We aimed to investigate whether human trabecular meshwork (TM) cells, the key cell type that regulates IOP, could support CMV replication, as well as demonstrate the relevant pathological changes in TM. When human TM cells were infected with CMV AD169, immediate early antigens were detected 1 day post-infection (dpi); cytopathic changes including rounding, a ballooned appearance with disorganization, and a decreased number of stress fibers were noted in TM cells. The marked increase in viral DNA accumulation was observed most notably at 5 and 7 dpi, suggesting that the active viral infection in human TM cells could be the key mechanism underlying the elevation of IOP in anterior viral uveitis. Notably, CMV infection enhanced the production of transforming growth factor (TGF)-β1, an upstream molecule that increases the resistance of the outflow pathway in human TM cells. The increase of TGF-β1 was countervailed by additional treatment with corticosteroids. Our results provide a pathogenic mechanism for IOP elevation in viral anterior uveitis.
authors.affiliation: Department of Ophthalmology, College of Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Republic of Korea.
authors.forename: Jin A
authors.initials: JA
authors.lastname: Choi
authors.affiliation: Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Ju-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Research Institute of St. Vincent Hospital, College of Medicine, Catholic University of Korea, Suwon, Republic of Korea.
authors.forename: Seung-Jun
authors.initials: SJ
authors.lastname: Noh
authors.affiliation: Department of Ophthalmology, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Eun
authors.initials: E
authors.lastname: Kyoung Kim
authors.affiliation: Department of Ophthalmology, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Chan Kee
authors.initials: CK
authors.lastname: Park
authors.affiliation: Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Soon-Young
authors.initials: SY
authors.lastname: Paik
mesh_terms: D000199:Actins / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D024042:Collagen Type I / Q000235:genetics / Q000276:immunology; D000090602:Collagen Type I, alpha 1 Chain; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D005353:Fibronectins / Q000235:genetics / Q000276:immunology; D015774:Ganciclovir / Q000494:pharmacology; D005786:Gene Expression Regulation; D005901:Glaucoma / Q000235:genetics / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007429:Intraocular Pressure; D008954:Models, Biological; D061251:Primary Cell Culture; D015398:Signal Transduction; D014129:Trabecular Meshwork / Q000187:drug effects / Q000473:pathology / Q000821:virology*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D014606:Uveitis, Anterior / Q000235:genetics / Q000276:immunology / Q000821:virology; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D000956:Antigens, Viral; C526317:CCN2 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D005353:Fibronectins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D003907:Dexamethasone; D015774:Ganciclovir