Title:Aminooxy-Acetic Acid Inhibits Experimental Autoimmune Uveitis by Modulating the Balance between Effector and Regulatory Lymphocyte Subsets
Volume: 20
Issue: 8
Author(s): Suyin Mei, Yike Huang, Na Li, Zongren Xu, Jing Xu, Qinjin Dai, Juan Wu, Aize Kijlstra, Peizeng Yang and Shengping Hou*
Affiliation:
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Eye Institute, Chongqing Key Laboratory of Ophthalmology, Chongqing,China
Keywords:
Experimental autoimmune uveitis, aminooxy-acetic acid (AOA), Th17 cell, Th1 cell, Treg cell, Uveitis.
Abstract: Purpose: A small molecular compound, aminooxy-acetic acid (AOA), has
been shown to modulate experimental autoimmune encephalomyelitis (EAE). The
current study was designed to investigate whether AOA has a similar effect on the
development of experimental autoimmune uveitis (EAU) and to further explore
underlying mechanisms of this drug.
Methods: EAU was induced in C57BL/6J mice by immunization with interphotoreceptor
retinoid-binding protein peptide 651-670 (IRBP 651-670). AOA (500μg or 750μg) or
vehicle was administered by intraperitoneal injection from day 10 to 14 after EAU
induction. The severity was assessed by clinical and histological scores. The integrity of
the blood retinal barrier was detected with Evans Blue. Frequencies of splenic Th1,
Th17 and Foxp3+ Treg cells were examined by flow cytometry. The production of
cytokines was tested by ELISA. The mRNA expression of IL-17, IFN-γ and IL-10 was
detected by RT-PCR. The expression of p-Stat1 and NF-κB was detected by Western
Blotting.
Results: AOA was found to markedly inhibit the severity of EAU, as determined by
clinical and histopathological examinations. AOA can relieve the leakage of blood retinal
barrier (BRB). Functional studies found a decreased frequency of Th1 and Th17 cells
and an increased frequency of Treg cells in EAU mice as compared with controls.
Further studies showed that AOA not only downregulated the production of the proinflammatory
cytokines including IFN-γ and IL-17 but also upregulated the expression of
an anti-inflammatory cytokine such as IL-10, which might be caused by inhibiting the
expressions of p-Stat1 and NF-κB.
Conclusion: This study shows that AOA inhibits the severity and development of EAU
by modulating the balance between regulatory and pathogenic lymphocyte subsets.
