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Anti-inflammatory effect of retinoic acid on experimental autoimmune uveoretinitis
  1. Hiroshi Keino*,
  2. Takayo Watanabe,
  3. Yasuhiko Sato,
  4. Annabelle A Okada, Dr
  1. 1 Kyorin University School of Medicine, Japan
  1. Correspondence to: Hiroshi Keino, Ophthalmology, Kyorin University School of Medicine, 6-20-2 Shinkawa Mitaka, Tokyo, 181-8611, Japan; keino{at}eye-center.org

Abstract

Aims: To determine whether an active metabolite of vitamin A, all-trans retinoic acid (ATRA), reduces inflammation in experimental autoimmune uveoretinitis (EAU).

Methods: Naive CD4+ T cells were activated with anti-CD3, anti-CD28 and TGF-β, in the presence or absence of ATRA. Intracellular expression of Foxp3 and IL-17 in the activated CD4+ T cells was assessed by flow cytometry. C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein (IRBP) peptide 1-20 (IRBP1-20). ATRA was administered intraperitoneally every other day (0.2 mg/mouse/day) from day 0 to day 21. In vivo-primed draining lymph node cells from vehicle-treated or ATRA-treated mice were stimulated with IRBP1-20 and culture supernatant was harvested for assay of IFN-γ and IL-17 by enzyme linked immunosorbent assay (ELISA).

Results: ATRA synergized with TGF-β to induce Foxp3+ T regulatory cells (Treg) and reciprocally inhibited development of Th17 cells induced by TGF-β and IL-6. ATRA treatment reduced the severity of EAU clinically and IFN-γ and IL-17 production were significantly reduced in ATRA-treated mice.

Conclusion: These findings demonstrate that ATRA treatment ameliorates severity of EAU and reduces the Th1/Th17 responses. ATRA may represent a new therapeutic modality for human refractory uveitis.

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