sodium-iodate and Retinitis

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.

Topics: Animals; Blood-Brain Barrier; Cells, Cultured; Endotoxemia; Female; Fibroblasts; Herpesviridae Infections; Immunosuppression Therapy; Iodates; Lipopolysaccharides; Lymphocytes; Macrophages; Mice; Mice, Inbred BALB C; Muromegalovirus; Retinitis; Virus Replication

To determine the role of retinal pigment epithelium in the induction of S-antigen-induced uveitis by administration of sodium iodate (NaIO3) to selectively damage the retinal pigment epithelium.. Forty-four Lewis rats were injected with 60 micrograms of S antigen in complete Freund's adjuvant. On postimmunization day 9 the rats were separated into four groups: three groups received NaIO3 at doses of 50, 25, and 10 mg/kg body weight, respectively, and the fourth group (control) received diluent. In addition, separate groups of animals (three in each group) received various doses of NaIO3 or diluent. All of the animals were killed on day 6 after NaIO3 injection, and the eyes were enucleated and submitted for light and electron microscopic examination. In addition, two groups of Lewis rats (6 in each group) were immunized with 0.5 ml of guinea pig spinal cord homogenate in complete Freund's adjuvant to induce experimental allergic encephalomyelitis. On postimmunization day 7, one group received NaIO3 at a dose of 50 mg/kg body weight, whereas the other group received diluent. All animals were killed between days 12 and 14, and spinal cord sections were obtained for microscopic examination.. In the control group immunized with S antigen, severe (2+ to 4+) uveoretinitis developed in 70% of the animals. In contrast, only 18% of the animals injected with NaIO3 at a dose of 50 mg/kg body weight exhibited disease, and this was a mild (1+) form. The groups injected with 25 mg/kg (1+ to 2+) and with 10 mg/kg (2+ to 3+) of NaIO3 showed a mild to moderate degree of uveoretinitis in 27% and 50% of the animals, respectively. In the remainder of the animals there was no evidence of uveoretinitis. All of the NaIO3-treated animals showed selective necrosis of the retinal pigment epithelium; this was extensive in the higher dose group and focal in the lower dose groups. In the experimental allergic encephalomyelitis model there was no significant difference in incidence or histologic appearance of demyelinating disease in NaIO3- vs diluent-treated groups.. These results indicate that the retinal pigment epithelium may play a role in the initiation and perpetuation of uveitis after sensitization with S antigen. The effect of NaIO3 appears to be localized to the retinal pigment epithelium; it had no effect on immune reactive cells, as evidenced by the development of experimental allergic encephalomyelitis in animals treated with NaIO3.

Topics: Animals; Antigens; Arrestin; Autoimmune Diseases; Encephalomyelitis, Autoimmune, Experimental; Enzyme-Linked Immunosorbent Assay; Eye Proteins; Female; Hypersensitivity, Delayed; Iodates; Lymphocyte Activation; Pigment Epithelium of Eye; Rats; Rats, Inbred Lew; Retinitis; Uveitis, Posterior

It is known that Brown Norway (BN) rats show resistance to the development of experimental autoimmune uveoretinitis (EAU). Although BN rats don't develop EAU easily when they were immunized with S antigen containing emulsified complete Freund's adjuvant, this paper reports on the development of EAU at the rate of 40-60% in BN rats when immunization is preceded by an injection of more than 0.5 mg (1.79 mg/kg of body wt) of sodium iodate which leads to the destruction of retinal pigment epithelium (RPE). It was thought that the destruction of RPE participated in the induction of EAU. Therefore, it is considered that the existence of RPE may play an important role in the induction of EAU.

Topics: Animals; Antigens; Arrestin; Autoimmune Diseases; Eye Proteins; Immunity, Cellular; Iodates; Male; Pigment Epithelium of Eye; Rats; Rats, Inbred BN; Retinitis; Uveitis

The hyperosmolarity-induced response of the ocular standing potential (SP) provides a method of testing the function of the retinal pigment epithelium (RPE) without using light stimulation. In this study, the changes in potential level occurring after a short-term intravenous injection of 10 ml of 20% mannitol were determined by means of a direct current amplifier for the following groups: Group 1, normal rabbit eyes; Group 2, rabbit eyes in which the RPE was damaged by sodium iodate; Group 3, rabbit eyes in which the photoreceptors were damaged by monoiodoacetic acid; Group 4, rabbit eyes with uveoretinitis experimentally induced by Arthus-type inflammation. The following results were obtained: 1. The hyperosmolarity-induced SP response consisted of a transient increase in potential level (positive wave) in Group 1. 2. For Group 2 a transient decrease in potential level (negative wave) was obtained, i.e., a reversal of the normal positive response to negative wave. 3. A positive wave and no reversal was found for Group 3. 4. For Group 4 a negative wave and a reversal of the normal response was obtained. These hyperosmolarity-induced SP responses provide additional information concerning the possibilities of the method for studying the function of the RPE.

Topics: Aging; Animals; Arthus Reaction; Electrophysiology; Electroretinography; Iodates; Iodoacetates; Iodoacetic Acid; Mannitol; Ocular Physiological Phenomena; Osmolar Concentration; Rabbits; Retinitis; Uveitis