Abstract

Cellular mechanisms in ocular immunologically mediated disease are being studied in animal models of experimental autoimmune uveoretinitis (EAU). Rats and mice are immunized with retinal-derived antigens, or synthetic peptides representing fragments of these antigens, to induce EAU. Susceptibility to disease is being evaluated in various strains of known genetic makeup in the hope of delineating the hereditary mechanisms that predispose to uveitis. EAU in rats and mice serves as a template for the evaluation of new drugs and compounds, as well as for the study and characterization of the participating cells and their factors. In vivo functional long-term T-cell lines and clones are developed from lymphoid organs of rats and mice immunized with uveitogenic ocular proteins. The functional properties and antigen receptors of these cells are studied to develop strategies for in vivo targeting of the autoimmune cells. The goal of these studies is to identify the immunogenetic factors predisposing to uveitic disease, learn about the pathogenic mechanisms involved, characterize the immunoreactive cells and their mediators, and finally to utilize this knowledge for designing rational approaches to immunotherapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Intramural Research (Z01)
Project #
1Z01EY000184-11
Application #
3777620
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Chen, Jun; Caspi, Rachel R; Chong, Wai Po (2018) IL-20 receptor cytokines in autoimmune diseases. J Leukoc Biol 104:953-959
St Leger, Anthony J; Hansen, Anna M; Karauzum, Hatice et al. (2018) STAT-3-independent production of IL-17 by mouse innate-like ?? T cells controls ocular infection. J Exp Med 215:1079-1090
Kielczewski, Jennifer L; Horai, Reiko; Jittayasothorn, Yingyos et al. (2016) Tertiary Lymphoid Tissue Forms in Retinas of Mice with Spontaneous Autoimmune Uveitis and Has Consequences on Visual Function. J Immunol 196:1013-25
Lee, Ellen J; Brown, Brieanna R; Vance, Emily E et al. (2016) Mincle Activation and the Syk/Card9 Signaling Axis Are Central to the Development of Autoimmune Disease of the Eye. J Immunol 196:3148-58
Silver, Phyllis B; Silver, Phyllis; Horai, Reiko et al. (2015) Retina-specific T regulatory cells bring about resolution and maintain remission of autoimmune uveitis. J Immunol 194:3011-9
Chong, Wai Po; Horai, Reiko; Mattapallil, Mary J et al. (2014) IL-27p28 inhibits central nervous system autoimmunity by concurrently antagonizing Th1 and Th17 responses. J Autoimmun 50:12-22
London, Anat; Benhar, Inbal; Mattapallil, Mary J et al. (2013) Functional macrophage heterogeneity in a mouse model of autoimmune central nervous system pathology. J Immunol 190:3570-8
Horai, Reiko; Silver, Phyllis B; Chen, Jun et al. (2013) Breakdown of immune privilege and spontaneous autoimmunity in mice expressing a transgenic T cell receptor specific for a retinal autoantigen. J Autoimmun 44:21-33
Kyger, Madison; Worley, Aneta; Huan, Jianya et al. (2013) Effective Arrestin-Specific Immunotherapy of Experimental Autoimmune Uveitis with RTL: A Prospect for Treatment of Human Uveitis. Transl Vis Sci Technol 2:1
Hansen, Anna M; Caspi, Rachel R (2009) Targeting lymphotoxin depletes pathogenic T cells. Nat Med 15:732-3

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