Aminoimidazole carboxamide ribonucleotide ameliorates experimental autoimmune uveitis

Jun Suzuki, Takeru Yoshimura, Marina Simeonova, Kimio Takeuchi, Yusuke Murakami, Yuki Morizane, Joan W. Miller, Lucia Sobrin, Demetrios G. Vavvas

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Abstract

PURPOSE. To investigate the anti-inflammatory effect of an adenosine monophosphate (AMP) analog, aminoimidazole carboxamide ribonucleotide (AICAR), in experimental autoimmune uveoretinitis (EAU). METHODS. C57BL/6 mice were injected daily with AICAR (200 mg/kg, intraperitoneally [IP]) from day 0, the day of interphotoreceptor retinoid-binding protein (IRBP) immunization, until day 21. The severity of uveitis was assessed clinically and histopathologically. T-cell proliferation and cytokine production of IFN-γ, IL-17, and IL-10 in response to IRBP stimulation were determined. In addition, regulatory T-cell (Treg) populations were measured. Co-stimulatory molecule expression (CD40, 80, 86, and I-Ab) on dendritic cells (DCs) in EAU and on bone marrow-derived dendritic cells (BMDCs) treated with AICAR was measured. RESULTS. AICAR treatment significantly reduced clinical and histologic severity of EAU as well as ocular cytokine production. An anti-inflammatory effect associated with the inhibition of T-cell proliferation and Th1 and Th17 cytokine production was observed. Increases in the Th2 response and Treg population were not observed with AICAR treatment. AICAR did significantly inhibit BMDC maturation by reducing co-stimulatory molecule expression. CONCLUSIONS. AICAR attenuates EAU by preventing generation of Ag-specific Th1 and Th17 cells. Impaired DC maturation may be an underlying mechanism for this anti-inflammatory effect observed with AICAR.

Original languageEnglish
Pages (from-to)4158-4169
Number of pages12
JournalInvestigative Ophthalmology and Visual Science
Volume53
Issue number7
DOIs
Publication statusPublished - Jun 2012
Externally publishedYes

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ASJC Scopus subject areas

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

Cite this

Suzuki, J., Yoshimura, T., Simeonova, M., Takeuchi, K., Murakami, Y., Morizane, Y., Miller, J. W., Sobrin, L., & Vavvas, D. G. (2012). Aminoimidazole carboxamide ribonucleotide ameliorates experimental autoimmune uveitis. Investigative Ophthalmology and Visual Science, 53(7), 4158-4169. https://doi.org/10.1167/iovs.11-9323