Home > Archive>Volume 17, Issue 2, 2024 >228-238. DOI:10.18240/ijo.2024.02.02
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N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats
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Corresponding Author:

Yan-Song Zhao. Department of Ophthalmology, Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province, China. zhaoyansong74@163.com; Xiao-Li Wang. School of Medical Imaging, Weifang Medical University, Weifang 261053, Shandong Province, China. wxlpine@163.com; Shu-Na Yu. Department of Anatomy, Weifang Medical University, Weifang 261053, Shandong Province, China. yushn@126.com

Fund Project:

Supported by the National Natural Science Foundation of China (No.82071888); the Natural Science Foundation of Shandong Province (No.ZR2021MH351; No.ZR2020MH074); the Introduction and Cultivation Project for Young Innovative Talents in Shandong Province; Weifang Science and Technology Development Plan (No.2021GX057).

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    Abstract:

    AIM: To observe the effects of N-acetylserotonin (NAS) administration on retinal ischemia-reperfusion (RIR) injury in rats and explore the underlying mechanisms involving the high mobility group box 1 (HMGB1)/receptor for advanced glycation end-products (RAGE)/nuclear factor-kappa B (NF-κB) signaling pathway. METHODS: A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye. Eighty male Sprague Dawley were randomly divided into five groups: sham group (n=8), RIR group (n=28), RIR+NAS group (n=28), RIR+FPS-ZM1 group (n=8) and RIR+NAS+ FPS-ZM1 group (n=8). The therapeutic effects of NAS were examined by hematoxylin-eosin (H&E) staining, and retinal ganglion cells (RGCs) counting. The expression of interleukin 1 beta (IL-1β), HMGB1, RAGE, and nod-like receptor 3 (NLRP3) proteins and the phosphorylation of nuclear factor-kappa B (p-NF-κB) were analyzed by immunohistochemistry staining and Western blot analysis. The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats. With NAS therapy, the HMGB1 and RAGE expression decreased significantly, and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression. Additionally, NAS exhibited an anti-inflammatory effect by reducing IL-1β expression. The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression, so as to the IL-1β expression and retinal edema, accompanied by an increase of RGCs in RIR rats. CONCLUSION: NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway, which may be a useful therapeutic target for retinal disease.

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Yu-Ze Zhao, Xue-Ning Zhang, Yi Yin,/et al.N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats. Int J Ophthalmol, 2024,17(2):228-238

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Publication History
  • Received:August 13,2023
  • Revised:November 07,2023
  • Online: January 22,2024
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