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Sheng-Li Cho, Chang-Hao Yang, I-Mo Fang; Inhibition of Experimental Autoimmune Anterior Uveitis by Chitosan Oligosaccharides. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6296.
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Acute anterior uveitis represents the most common form of uveitis. NF-κB is a key transcription factor in uveitis immunopathogenesis. Chitosan oligosaccharides (COS) is used as a dietary supplement with various biological activities. Recent studies have shown that COS reduces NF-κB activation and retinal oxidative damage in vivo. This study was performed to determine whether COS is effective in inhibiting anterior uveitis in a rat model.
To induce experimental autoimmune anterior uveitis (EAAU), Lewis rats were injected in the hind foodpad with a single dose of unveitogenic melanin-associated antigen. One day after immunization, a low or high dose (5 or 10 mg/kg) of chitosan was administered intragastrically for 14 days, while PBS was administered as a control. Clinical activity scores of EAAU were evaluated daily using a slit lamp biomicroscope. On day 14, eyes were harvested for histological analysis of iris/ciliary body tissues. We collected aqueous humor for the quantification of inflammatory cells. Western blotting and ELISA were also performed to determine the levels of pro-inflammatory chemokines ICAM-1, iNOS, MCP-1, RANTES, fractalkine, and TNF-α. Furthermore, NF-κB activity was assessed from nuclear extract from iris/ciliary body tissues by electrophoretic mobility shift assay (EMSA).
Treatment with COS significantly inhibited the development of ocular inflammation when compared with treatment with control PBS. We demonstrated that COS treatment significantly attenuated clinical activity scores in rats with EAAU. Furthermore, COS treatment effectively decreased leukocyte infiltration in the iris/ciliary body. The number of inflammatory cells in the aqueous humor was reduced by COS in a dose dependent manner. COS dose dependently decreased the levels of ICAM-1, TNF-α, iNOS, MCP-1, RANTES, and fractalkine in iris/ciliary body. Finally, EMSA demonstrated that NF-κB activation was inhibited by COS.
This study found that COS administration appeared to be effective in inhibiting ocular inflammation in the EAAU model. This effect in the anterior segment of the eye may be, at least in part, modulated through blocking the NF-κB signaling pathway. Therefore, COS is probably valuable for the therapy of ocular inflammatory disorders such as acute anterior uveitis.
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