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Title: Immunomodulation of experimental autoimmune uveitis
Author: Dua, Harminder Singh
ISNI:       0000 0001 2448 2196
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1992
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Chronic posterior uveitis is a relatively common clinical disorder and an importance cause of visual impairment in young adults. Experimental autoimmune uveitis (EAU) and its associated experimental autoimmune pinealitis (EAP) induced by retinal autoantigens are predominantly CD4+ T cell mediated (auto) immune disease of the retina and uveal tract of the eye and the pineal gland respectively. EAU bears a close clinical and pathological resemblance to chronic posterior uveitis in humans and seves as a good animal model for the study of posterior uveitis. The EAU model was used to study means of modulating the host's immune response to suppress or inhibit the onset of uveitis. The onset of retinal S-antigen induced EAU could be successfully inhibited by pre-treating Lewis rats with a retinal S-antigen (carboxy terminus) specific monoclonal antibody called S2.4.C5. This however did not suppress the associated EAP indicating that the monoclonal antibody acted via the efferent arc of the immune mediated response. This prompted a study of the 'Blood-retinal and Blood-pineal barrier sites' during the active stages of EAU and EAP. Transmission electron microscopy of the vascular endothelium revealed changes resembling 'High endothelial venules' of lymph nodes in the retinal and pineal vasculature. In an attempt to identify one or more immunodominant epitopes of S-antigen that may be relevant to tolerance induction, an in-vitro and in-vivo study using enzyme digested preparations of S-antigen was carried out. This revealed that digestion of S-antigen by a protease derived from staphylococcus aureus V8 strain, not only inhibited the binding of the monoclonal S2.4.C5 in-vitro but was also associated with an in-vivo attenuation of the pathogenic response to S-antigen indicating that a dominant immunogenic epitope of S-antigen was located at the C-terminus of the molecule.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Uveal inflammation