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The effect of spleen tyrosine kinase inhibitor R406 on diabetic retinopathy in experimental diabetic rats

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Abstract

Purpose

To investigate the effect of spleen tyrosine kinase (Syk) inhibitor R406 on diabetic retinopathy (DR) in diabetic mellitus (DM) rats.

Methods

Rats were randomized into Normal, DM, DM + 5 mg/kg R406 and DM + 10 mg/kg R406 groups. DM rats were established via injection of streptozotocin (STZ). One week after model establishment, rats in treatment groups received 5 mg/kg or 10 mg/kg R406 by gavage administration for 12 weeks consecutively, followed by the detection with hematoxylin-eosin (HE) staining, Evans blue angiography, retinal trypsin digestion assay, Western blotting, immunohistochemistry, TUNEL assay, immunofluorescence assay and quantitative reverse transcriptase real-time polymerase chain reaction (qRT-PCR).

Results

The retina of DM rats presented different degree of edema, disordered and loose structure, swollen cells with enlarged intercellular space, and dilated and congested capillaries. Besides, the retinal vessels of DM rats showed high fluorescence leakage. However, R406 alleviated the above-mentioned conditions, which was much better with high concentration of R406 (10 mg/kg). R406 also reversed the down-regulations of occludin, claudin-5, ZO-1 and the up-regulation of and VEGF in retinal tissues of DM rats; inhibited retinal cell apoptosis; strengthened retinal cell proliferation; and reduced expressions of IL-1β, IL-6, TNF-α and nuclear p65 NF-κB in retinal tissues. The improvement in all these indexes was much more significant in rats of DM + 10 mg/kg R406 group than in rats of DM + 5 mg/kg R406 group.

Conclusion

Syk inhibitor R406 could attenuate retinal inflammation in DR rats via the repression of NF-κB activation.

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Authors and Affiliations

  1. Department of Ophthalmology, The First Hospital of Shijiazhuang City, No. 12, Pingan North Street, Shijiazhuang, 050000, Hebei Province, China

    Xian Su, Zhao-Hui Sun, Qian Ren, Li Yin, Na Liang, Ling Meng & Rui-Xue Sun

  2. Department of Ophthalmology, The Third Hospital of Shijiazhuang City, Shijiazhuang, 050011, Hebei Province, China

    Jun-Ru Liu

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  1. Xian Su
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Correspondence to Rui-Xue Sun.

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The study conformed to the Guide for the Care and Use of Laboratory Animals [40], and all animal experiments were conducted with the approval of Medical Ethics Committee of Laboratory Animals in the First Hospital of Shijiazhuang City.

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Su, X., Sun, ZH., Ren, Q. et al. The effect of spleen tyrosine kinase inhibitor R406 on diabetic retinopathy in experimental diabetic rats. Int Ophthalmol 40, 2371–2383 (2020). https://doi.org/10.1007/s10792-020-01422-4

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