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L. J. Karren, G. G. Burrows, J. Mooney, G. Adamus; Suppression of Acute and Recurrent IRBP-Induced Experimental Autoimmune Uveitis by Recombinant TCR Ligand in Lewis Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4767.
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To examine the effectiveness of Recombinant T-cell Receptor ligands (RTLs) in the treatment of acute and recurrent EAU induced with IRBP peptide.
We designed and tested RTL220 containing the α1 and β1 domains of MHC class II molecules linked to the uveitogenic IRBP 1177-1191 peptide in Lewis rats. EAU was induced by subcutaneous injection of 20 µg IRBP1177-1191 peptide in complete Freund’s adjuvant and M. Tuberculosis at 2 mg/ml. Recurrent EAU was induced by passive transfer of 5x106 IRBP1177-1191 peptide-specific and activated T cells. Uveitis was examined by clinical and histological scoring.
We designed different regiments of treatment with RTL220. The RTL220 treatment (0.3 mg/dose for 5 days) beginning on day 1 resulted in a delayed onset, a significant reduction in acute EAU severity, and showed protection of the retina from inflammatory damage. Treatment beginning at clinical onset was the most effective, showing complete protection from EAU at the clinical and histological levels. In addition, RTL220 protected the rats receiving passively transferred specific T cells from recurrent uveitis. Five-days of treatment applied at the time of the first bout followed by boosts once a week were effective in the prevention of subsequent attacks. Histological examination showed reduced migration of inflammatory cells into the eye or complete protection with significantly reduced pro-inflammatory cytokines.
RTL220 can prevent and reverse clinical and histological EAU by preventing the recruitment of inflammatory cells into the eye. These findings suggest a possible clinical application of this novel class of peptide/MHC class II drugs for patients with posterior autoimmune uveitis.
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