March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Aminoimidazole Carboxamide Ribonucleotide (AICAR) Ameliorate Experimental Autoimmune Uveitis
Author Affiliations & Notes
  • Jun Suzuki
    Ophthalmology, Angiogensis Lab, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Takeru Yoshimura
    Vascular Biology Program and Department of Surgery, Childrens’ Hospital Boston, Boston, Massachusetts
  • Marina Simeonova
    Ophthalmology, Angiogensis Lab, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Kimio Takeuchi
    Ophthalmology, Angiogensis Lab, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Yusuke Murakami
    Ophthalmology, Angiogensis Lab, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Yuki Morizane
    Ophthalmology, Angiogensis Lab, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Joan W. Miller
    Ophthalmology, Angiogensis Lab, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Lucia Sobrin
    Ophthalmology, Angiogensis Lab, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Demetrios G. Vavvas
    Ophthalmology, Angiogensis Lab, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Jun Suzuki, None; Takeru Yoshimura, None; Marina Simeonova, None; Kimio Takeuchi, None; Yusuke Murakami, None; Yuki Morizane, None; Joan W. Miller, None; Lucia Sobrin, None; Demetrios G. Vavvas, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 2762. doi:
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      Jun Suzuki, Takeru Yoshimura, Marina Simeonova, Kimio Takeuchi, Yusuke Murakami, Yuki Morizane, Joan W. Miller, Lucia Sobrin, Demetrios G. Vavvas; Aminoimidazole Carboxamide Ribonucleotide (AICAR) Ameliorate Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2762.

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

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Abstract

Purpose: : To investigate the anti-inflammatory effect of the AMP analog, aminoimidazole carboxamide ribonucleotide (AICAR) in experimental autoimmune uveoretinitis (EAU).

Methods: : EAU was induced in C57BL/6 mice via immunization by interphotoreceptor retinoid-binding protein (IRBP). AICAR (200mg/kg, intraperitoneally) was given daily for 3 weeks starting on the day of EAU induction. Severity of uveitis was assessed clinically and histopathologically. T cell proliferation and cytokine production of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-10 and IL-17 against IRBP stimulation and regulatory T cell (Treg) populations WERE measured. Co-stimulatory molecule expression (CD40, 80, 86 and I-Ab) on the dendritic cells in EAU and bone marrow-derived dendritic cells (BMDC) treated with AICAR was assessed.

Results: : AICAR treatment significantly reduced clinical and histological severity of EAU (2.6 ± 0.70 and 1.65 ± 0.68 vs 1.32 ± 0.95 and 0.53 ± 0.73, p<0.001) as well as ocular cytokine production. Anti-inflammatory effects associated with the inhibition of T cell proliferation and Th1 and Th17 cytokine production were observed. Neither the Th2 response nor Treg population were elevated by AICAR administration. AICAR administration significantly inhibited BMDC maturation by reducing co-stimulatory molecule expression.

Conclusions: : AICAR attenuates EAU by preventing generation of Ag-specific Th1 and Th17 cell induction possibly through impaired DC maturation.

Keywords: uveitis-clinical/animal model • autoimmune disease • immunomodulation/immunoregulation 
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