Abstract
FTY720 has shown a protective effect in several diseases via inhibiting inflammation and decreasing vascular permeability. The purpose of this study was to assess the impact of FTY720 on inflammation and the blood-retinal barrier (BRB) in diabetic rats. Male Wister rats were induced to develop diabetes by streptozotocin, and FTY720 was administered by oral gavage daily for 12 weeks. All experiments were performed at 12 weeks after model establishment. Gene expression was assessed by real-time PCR. Protein expression and/or distribution were assessed by Western blotting and/or immunohistochemistry. The BRB breakdown was determined by staining of retinal whole mounts and quantified using Evans blue. FTY720 induced lymphopenia in diabetic rats. Proinflammatory cytokines (TNF-α, IL-6, and IL-1β) and adhesion molecules (inter-cellular cell adhesion molecule-1 and vascular cell adhesion molecule-1) were increased in retinas of diabetic rats. FTY720 significantly inhibited the up-regulation of these inflammatory factors. FTY720 also suppressed nuclear factor-κB activation seen in retinas of diabetic rats. Additionally, FTY720 prevented BRB breakdown and reduction of tight junction proteins (ZO-1, Occludin, and Claudin-5) in the retinas of diabetic rats. Down-regulation of S1P1 and S1P3 was also reversed by FTY720 in retinas of diabetic rats. FTY720 provides protection against diabetic retinopathy (DR), which may involve its anti-inflammatory and barrier-enhancing effects. The S1PR modulation may serve as a novel approach to treat patients with DR.
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