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Title: Characterisation of autoimmune ocular disease induced by retinol binding protein-3
Author: Boldison , Joanne
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2011
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Experimental Autoimmune Uveitis (EAU) serves as a model for human non-infectious intraocular inflammation, This CD4+ T cell mediated disease can be induced with peptides from the retinal autoantigen retinol binding protein 3 (RBP-3), Antigen specific CD4+ T cells orchestrate disease leading to a variation in the population of cells infiltrating the retina at different stages of inflammation. Infiltrating activated macrophages cause tissue destruction by release of reactive oxygen species, leading to retinal damage. T cell epitopes can influence effector cells and inflammation, though only a few uveitogenic epitopes have been described in the C57BLl6 mouse. The study of population dynamics of EAU induced with recombinant protein subunits of RBP-3 allowed the identification of a novel uveitogenic peptide in subunit 3 of RBP-3 protein. RBP-3 peptide 629-641 induced EAU in this model, as demonstrated by fundal imaging and retinal cellular analysis by flow cytometry. The C57BU6 model is a mild chronic and persistent inflammatory disease; extensive characterization of infiltrate within the retina in this model is described in this thesis. Post primary peak the infiltrate in the inflamed eye has a significant increase of CD4+ I L-17 produCing cells compared to the spleen. Also demonstrated was a late increase in numbers of CD8+ T cells which expressed low levels of IFNy and IL-17 and lacked the ability to degranulate as determined by CD107a ·expression. Coinciding with the increase in CD8+ T cells was an increase in cytotoxic CD1 07a+ NK cells. This analysis revealed distinct changes in the leukocyte cell populations and microenvironment at the late persistent phase of disease that may regulate or perpetuate chronic EAU.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available