April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Vitamin A Deficiency Hinders The Development Of Experimental Autoimmune Uveitis
Author Affiliations & Notes
  • Ru Zhou
    National Eye Institute/NIH, Bethesda, Maryland
  • Reiko Horai
    National Eye Institute/NIH, Bethesda, Maryland
  • WaiPo Chong
    National Eye Institute/NIH, Bethesda, Maryland
  • Carlos Rodrigo Zarate-Blades
    National Eye Institute/NIH, Bethesda, Maryland
  • Jun Chen
    National Eye Institute/NIH, Bethesda, Maryland
  • Phyllis B. Silver
    National Eye Institute/NIH, Bethesda, Maryland
  • Rachel R. Caspi
    National Eye Institute/NIH, Bethesda, Maryland
  • Footnotes
    Commercial Relationships  Ru Zhou, None; Reiko Horai, None; WaiPo Chong, None; Carlos Rodrigo Zarate-Blades, None; Jun Chen, None; Phyllis B. Silver, None; Rachel R. Caspi, None
  • Footnotes
    Support  NIH Intramural support
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2939. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Ru Zhou, Reiko Horai, WaiPo Chong, Carlos Rodrigo Zarate-Blades, Jun Chen, Phyllis B. Silver, Rachel R. Caspi; Vitamin A Deficiency Hinders The Development Of Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2939.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : An active metabolite of vitamin A (VitA), all-trans retinoic acid (ATRA), can synergize with TGF-beta to induce Foxp3+ regulatory T cells (Treg) and inhibit IL-17-producing Th17 cells. Others reported that augmentation of VitA by treatment with ATRA or its receptor-specific agonist reduces inflammation in experimental autoimmune uveitis (EAU) at least in part by enhancing Treg cells. We therefore hypothesized that systemic depletion of VitA will inhibit Treg induction and enhance disease.

Methods: : To generate VitA deficient (VAD) mice, pregnant B10.RIII females were fed a VitA deficient diet from day 14 of gestation. Pups continued to be maintained on the same diet. To assess intraocular Treg conversion, IRBP-specific naïve T cells were injected into eyes of VAD mice. In vitro, CD4+ T cells were activated under neutral or Th1-, Th17-polarizing conditions. In vivo, VAD mice were immunized with the uveitogenic peptide IRBP161-180. Expression of Foxp3, IL-17, or IFN-γ in CD4+ T cells were assessed by intracellular staining. Cell proliferation was detected by 3H-thymidine uptake. Cell culture supernatants were assayed for IL-17 and IFN-γ by ELISA.

Results: : Surprisingly, VAD mice were resistant to EAU induction. Compared to mice fed control diet, VAD mice had significantly reduced conversion of conventional T cells to FoxP3+ Tregs locally in the eye but, unexpectedly, they showed a higher ratio of FoxP3+ Treg to T effector CD4+ T cells in the periphery. Proliferation to IRBP in vitro of whole lymph node cells from IRBP-immunized VAD mice was not reduced, but Ag specific production of IL-17 and IFN-γ were drastically diminished.

Conclusions: : Despite defective Treg conversion in the eye, VAD mice still have peripheral Tregs. Reduction in Th1 and Th17 responses without reduction of Ag specific proliferation suggest that resistance of VAD mice to EAU may reflect a defect in effector T cell generation under conditions of VitA deficiency that is unconnected to inhibition by Tregs.

Keywords: vitamin A deficiency • immunomodulation/immunoregulation • autoimmune disease 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.