Dissertation/Thesis Abstract

Role of complement and complement regulatory proteins in experimental autoimmune anterior uveitis (EAAU)
by Manickam, Balasubramanian, Ph.D., University of Arkansas for Medical Sciences, 2009, 154; 3357548
Abstract (Summary)

The role of complement system in ocular diseases has drawn a lot of attention in the past decade. Experimental Autoimmune Anterior Uveitis (EAAU) is an animal model for Idiopathic Anterior Uveitis in humans. We have previously shown that complement activation plays a critical role in the development of experimental autoimmune anterior uveitis (EAAU). One of the objectives of the current study was to delineate the pathway of complement activation that is crucial for the induction of EAAU. Our results clearly demonstrate that alternative pathway of complement activation is the key player in induction of EAAU and specific blockade of this pathway could be a potential therapeutic target in the treatment of EAAU. We have also demonstrated that the suppression of complement regulatory protein (CReg) - Crry exacerbated EAAU. Based on our published results, we hypothesized that exogenous administration of recombinant soluble Crry-Ig, a complement regulatory protein will ameliorate EAAU. Our data suggested that inhibition of C3 activation using recombinant inhibitors can be therapeutically useful in both prevention and treatment of EAAU. This finding has important clinical implications because current therapeutic strategies to treat AU are only palliative and not curative. EAAU is characterized by the infiltration of inflammatory cells in iris, CB and the anterior chamber of the eye. We next investigated the role of complement activation products C3a, C5a and MAC in the induction of EAAU. Our results clearly suggest that C3a, C5a and MAC are not the major players in the pathogenesis of EAAU. In conclusion, the evidence from the present study clearly demonstrates that complement system and CRegs play a key role in the pathogenesis of EAAU. We believe that therapy based on complement inhibition has great potential in future for the treatment of idiopathic anterior uveitis (AU), untreated AU leads to blindness.

Indexing (document details)
Advisor: Bora, Nalini S.
Commitee:
School: University of Arkansas for Medical Sciences
School Location: United States -- Arkansas
Source: DAI-B 70/04, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Ophthalmology, Pathology, Immunology
Keywords: Anterior uveitis, Autoimmunity, EAAU, Experimental autoimmune anterior uveitis, Inflammation
Publication Number: 3357548
ISBN: 9781109148244
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