Abstract
We investigated the protective effects and mechanisms of chitosan oligosaccharides (COS) on experimental autoimmune anterior uveitis (EAAU) in rats. EAAU was induced in Lewis rats by footpad and intraperitoneal injections of melanin-associated antigen. The rats received intraperitoneal injections of low-dose (5 mg/kg) or high-dose (10 mg/kg) COS or PBS daily after the immunization. The effects of COS were evaluated by determining the clinical scores and the morphology of the iris/ciliary body (ICB). The expression of inflammatory mediators was evaluated using western blot, immunofluorescence, and ELISA. Treatment with COS significantly attenuated the clinical scores and the leukocyte infiltration in the ICB in a dose-dependent manner. COS effectively reduced the expression of inflammatory mediators (TNF-α, iNOS, MCP-1, RANTES, fractalkine, and ICAM-1). Moreover, COS decreased the IκB degradation and p65 presence in the ICB, which resulted in the inhibition of NF-κB/DNA binding activity. In an in vitro study, sensitized spleen-derived lymphocytes of the COS-treated group showed less chemotaxis toward their aqueous humor and decreased secretion of the above inflammatory mediators in the culture media. COS treated EAAU by inhibiting the activation of NF-κB and reducing the expression of inflammatory mediators. COS might be a potential treatment for acute anterior uveitis.
Highlights
Acute anterior uveitis (AAU) is the most common uveitis in humans
We found that chitosan oligosaccharides (COS) suppressed NF-κB activation by inhibiting IκB degradation and p65 translocation, which might contribute to the decreased proinflammatory cytokine and chemokine production observed in experimental autoimmune anterior uveitis (EAAU)
We showed that COS could decrease the production of TNF-α, MCP-1, RANTES, fractalkine, and Nitric Oxide (NO) in the iris/ciliary body (ICB) in a dose-dependent manner, which might counteract the inflammatory response by inhibiting leukocyte recruitment into the eye
Summary
Acute anterior uveitis (AAU) is the most common uveitis in humans. AAU can cause significant visual problems because of its recurrent nature and might result in secondary complications, such as cataract formation, cystoid macular edema, and glaucoma [1]. The exact mechanism of AAU remains unknown. Topical corticosteroids are generally the mainstay in the treatment of AAU; periocular injections and systemic steroids are necessary in recalcitrant cases. The long-term use of corticosteroids might produce a wide range of systemic and ocular side effects [2]. There is increasing interest in therapies with new molecules that eliminate the side effects of corticosteroids but are as efficient in reducing ocular inflammation and preventing tissue destruction
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