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      Use of Optical Coherence Tomography and Electroretinography to Evaluate Retinal Pathology in a Mouse Model of Autoimmune Uveitis

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          Abstract

          Experimental autoimmune uveoretinitis (EAU) in mice is a model for human autoimmune uveitis. Longitudinal follow-up is only possible by non-invasive techniques, but the information obtained by visual fundus examination can be limited. We therefore evaluated the efficacy of optical coherence tomography (OCT) and electroretinography (ERG) to monitor pathological and functional changes of the retina in vivo. OCT imaging and ERG recording as a measure of visual function were compared with visual fundoscopic imaging and histology findings in the same mouse. Our results showed that OCT imaging of the retina was well correlated with clinical and histological observations in mice during EAU. However, OCT imaging was more sensitive than fundoscopic imaging in detecting the cell infiltrates at the early phase of disease onset. Furthermore, by allowing multi-layer cross- and horizontal-sectional visualizations of retinal lesions longitudinally in a noninvasive fashion, OCT added information that could not be obtained by fundoscopic and histological examinations. Lastly, retinal thickness obtained by OCT imaging provided a key indicator reflecting disease activity, which showed a close association with visual dysfunction as measured by ERG recordings in EAU mice. Thus, our findings demonstrate that OCT is a highly sensitive and reliable technique, and a valuable method for the semi-quantitative evaluation of retinal inflammation in vivo in the mouse.

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          Optical coherence tomography.

          A technique called optical coherence tomography (OCT) has been developed for noninvasive cross-sectional imaging in biological systems. OCT uses low-coherence interferometry to produce a two-dimensional image of optical scattering from internal tissue microstructures in a way that is analogous to ultrasonic pulse-echo imaging. OCT has longitudinal and lateral spatial resolutions of a few micrometers and can detect reflected signals as small as approximately 10(-10) of the incident optical power. Tomographic imaging is demonstrated in vitro in the peripapillary area of the retina and in the coronary artery, two clinically relevant examples that are representative of transparent and turbid media, respectively.
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            Ultrahigh-resolution ophthalmic optical coherence tomography.

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              A new model of autoimmune disease. Experimental autoimmune uveoretinitis induced in mice with two different retinal antigens.

              Experimental autoimmune uveoretinitis (EAU) is an organ-specific, T lymphocyte-mediated autoimmune disease, which serves as a model for several human ocular inflammations of an apparently autoimmune nature. EAU pathology in some rodents and in monkeys can readily be induced by immunization with several different retinal proteins; however, advancing research into the cellular mechanisms of this disease has raised the need for an EAU model in an immunologically and genetically well defined species. We report here the induction of EAU in the mouse, which has hitherto been considered a species refractory to EAU, with two retinal Ag, the retinal soluble Ag and the interphotoreceptor retinoid-binding protein. Although all the mouse strains tested exhibited lymphocyte responses and antibody titers to both retinal Ag, EAU was inducible in only some of the strains, and the uveitogenic responses to retinal soluble Ag and interphotoreceptor retinoid-binding protein appeared to be mutually exclusive. The EAU model in mice was found to differ in several respects from the EAU model in other rodent species. Induction of the disease was achieved with a relatively high dose of Ag and an intensified immunization protocol, and the onset of disease was later, the duration was longer, and the course was less acute. Anterior segment involvement was slight or nonexistent, and damage to the retina and uvea was of a focal rather than of a diffuse nature. Murine EAU appeared to approximate some types of human uveitis more closely than the EAU models described in other rodent species with respect to its pathologic manifestations as well as its more chronic course. The relatively longer duration of the active stage of disease in murine EAU should facilitate therapeutic intervention in established disease, which was not feasible in the more acute models of EAU. The extensive knowledge of the immunologic parameters of the mouse and the availability of genetically defined strains should be of great value in the study of cellular mechanisms and immunogenetics of ocular autoimmune disease.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                14 May 2013
                : 8
                : 5
                : e63904
                Affiliations
                [1 ]Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United Sates of America
                [2 ]Vision Function Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United Sates of America
                Justus-Liebig-University Giessen, Germany
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JC RRC. Performed the experiments: JC HQ RH. Analyzed the data: JC CCC HQ. Contributed reagents/materials/analysis tools: HQ RH. Wrote the paper: JC RRC.

                [¤]

                Current address: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China

                Article
                PONE-D-13-02065
                10.1371/journal.pone.0063904
                3653843
                23691112
                0c485644-07c3-4246-b604-b5eb735cb047
                Copyright @ 2013

                This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 12 January 2013
                : 8 April 2013
                Page count
                Pages: 8
                Funding
                This work was supported by NIH-National Eye Institute Intramural funding, grant #EY000184. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Immunology
                Autoimmunity
                Model Organisms
                Animal Models
                Mouse
                Medicine
                Clinical Immunology
                Autoimmune Diseases
                Clinical Research Design
                Animal Models of Disease
                Ophthalmology
                Retinal Disorders

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                Uncategorized

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