title: Murine cytomegalovirus (MCMV) spreads to and replicates in the retina after endotoxin-induced disruption of the blood-retinal barrier of immunosuppressed BALB/c mice.
abstract: The goal of this study was to determine whether disruption of the blood-retinal barrier (BRB) facilitates spread of MCMV to the retina in immunosuppressed (IS) BALB/c mice. IS mice were inoculated intravenously (i.v.) with murine cytomegalovirus (MCMV) or with macrophages infected with MCMV for 4 days in vitro. The BRB was disrupted by injection of sodium iodate (i.v.) or lipopolysaccharide (LPS, i.v. or anterior chamber). Frozen sections of ocular tissue were examined for MCMV antigens. The results showed that MCMV-infected cells were observed only in the choroid and ciliary body in IS mice with an intact BRB. After LPS injection, a few positive cells were observed in the retina of IS mice after i.v. injection of MCMV. In lipopolysaccharide (LPS)-treated IS mice, a few PKH-26-positive macrophages or MCMV-positive cells were observed in the retina at 1 or 2 days after injection of macrophages. No PKH-26-positive cells or virus-infected cells were noted in the retina of phosphate-buffered saline (PBS)-treated mice. Ten days after injection of virus-infected macrophages, MCMV-infected cells were observed in choroid and ciliary body of both LPS- and PBS-treated mice, but they were observed in the retina only in LPS-treated mice. The results support the idea that disruption of the BRB allows MCMV to spread to the retina of IS mice and that monocytes/macrophages disseminate MCMV to the retina in mice with a disrupted BRB. By extrapolation, damage to the BRB in immunosuppressed patients may facilitate spread of CMV-infected monocytes/macrophages to the retina.
authors.affiliation: Department of Cellular Biology and Anatomy, The Medical College of Georgia, Augusta, Georgia 30912, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Xin
authors.forename: Sally S
authors.initials: SS
authors.lastname: Atherton
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D002478:Cells, Cultured; D019446:Endotoxemia / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology*; D007165:Immunosuppression Therapy; D007452:Iodates / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology / Q000821:virology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000254:growth & development*; D012173:Retinitis / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication / Q000276:immunology
chemical_list: D007452:Iodates; D008070:Lipopolysaccharides; C032285:sodium iodate