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Anti-inflammatory effect of retinoic acid on experimental autoimmune uveoretinitis
  1. Hiroshi Keino1,
  2. Takayo Watanabe1,
  3. Yasuhiko Sato2,
  4. Annabelle A Okada1
  1. 1Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan
  2. 2Division of Radioisotope Research, Kyorin University School of Medicine, Tokyo, Japan
  1. Correspondence to Dr Hiroshi Keino, Department of Ophthalmology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan; keino{at}


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 transforming growth factor (TGF)-β, in the presence or absence of ATRA. Intracellular expression of transcription factor forkhead box P3 (Foxp3) and interleukin (IL)-17 in the activated CD4+ T cells was assessed by flow cytometry. C57BL/6 mice were immunised with human interphotoreceptor retinoid binding protein peptide 1–20 (IRBP1–20). ATRA was administered intraperitoneally every other day (0.2 mg/mouse per 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 the culture supernatant fraction was harvested for assay of interferon (IFN)-γ and IL-17 by ELISA.

Results ATRA synergised with TGF-β to induce Foxp3+ T regulatory cells (Treg) and reciprocally inhibited development of IL-17-producing T helper cells (Th17) 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.

  • Experimental autoimmune uveoretinitis
  • all-trans retinoic acid
  • Th17
  • Treg
  • immunology
  • treatment medical
  • experimental and animal models

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  • Funding This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

  • Competing interests None.

  • Ethics approval Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.