A promising therapeutic approach for treatment of posterior uveitis: Recombinant T cell receptor ligand protects lewis rats from acute and recurrent experimental autoimmune uveitis

Grazyna Adamus, Landon J. Karren, Jeff Mooney, Gregory G. Burrows

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Introduction: Chronic autoimmune uveitis is a major cause of vision loss from intraocular inflammation in humans. In this study we report that a recombinant TCR ligand (RTL220) composed of the α1 and β1 domains of MHC class II molecules linked to the uveitogenic interphotoreceptor retinoid-binding protein (IRBP) 1177-1191 peptide is effective in the suppression of acute and recurrent experimental autoimmune uveitis (EAU). Material and Methods: EAU was induced with IRBP1177-1191 peptide or by adoptive transfer of specific T cells in Lewis rats. The rats received 5 doses of RTL220 subcutaneously every other day starting at the onset of clinic signs of EAU. Results: The administration of RTL220 resulted in a delayed onset and a significant amelioration of the disease severity at clinical levels and showed protection of the retina from inflammatory damage at histological levels. In treatment of recurrent EAU, RTL220 administrated at the first or second onset of clinical disease significantly inhibited EAU, modulated immune responses and provided protection from relapses of uveitis. The systemic and local proinflammatory cytokines were significantly reduced, including IL-17. There was local and systemic increase in IL-10 and reduction in the expression of the proinflammatory chemokines CCL2, CCL3 and CCL5. Conclusions: Our studies demonstrate a successful treatment of acute and recurrent EAU with RTL220, which effectively suppressed the recurrence of inflammation and reversed clinical and histological EAU by altering cytokine and chemokine expression. These findings strongly support a possible clinical application of this novel class of peptide/MHC class II drugs for patients with autoimmune uveitis.

Original languageEnglish (US)
Pages (from-to)24-33
Number of pages10
JournalOphthalmic Research
Volume44
Issue number1
DOIs
StatePublished - Jun 2010

Fingerprint

Posterior Uveitis
Uveitis
T-Cell Antigen Receptor
Ligands
Therapeutics
Peptides
Cytokines
Inflammation
Chemokine CCL3
Recurrence
Chemokine CCL5
Interleukin-17
Adoptive Transfer
Chemokine CCL2
Chemokines
Interleukin-10
Retina

Keywords

  • Chemokine
  • Cytokine
  • Experimental autoimmune uveitis
  • Rat
  • RTL
  • Treatment

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

A promising therapeutic approach for treatment of posterior uveitis : Recombinant T cell receptor ligand protects lewis rats from acute and recurrent experimental autoimmune uveitis. / Adamus, Grazyna; Karren, Landon J.; Mooney, Jeff; Burrows, Gregory G.

In: Ophthalmic Research, Vol. 44, No. 1, 06.2010, p. 24-33.

Research output: Contribution to journalArticle

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