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<p>Astrocyte-mediated neuroinflammation has recently been implicated as a key contributor to neurodegeneration following retinal ischemia–reperfusion (IR) injury. However, the role of miR‑16‑5p in this process remains unclear. This study aimed to investigate the function and mechanism of miR‑16‑5p. TargetScan was used to predict miR-16-5p targets, which were validated by RNA pull-down. miR‑16‑5p expression was assessed by RT‑qPCR in IR retinas and in astrocytes after oxygen–glucose deprivation/reoxygenation (OGD/R). Astrocyte activation, inflammatory cytokine, and Wip1/nuclear factor kappa B (NF‑κB) signaling were examined following miR-16-5p modulation with mimics or inhibitors <i>in vitro</i> and <i>in vivo</i>. Retinal ganglion cell (RGC) apoptosis, retinal function, and morphology were evaluated. miR‑16‑5p was found to potentially target wild-type p53-induced phosphatase 1 (Wip1) and decreased Wip1 expression. In IR-injured mouse retinas and OGD/R-treated astrocytes, miR‑16‑5p expression was significantly downregulated. This decrease was accompanied by astrocyte activation, increased TNF-α and IL-1β levels, and upregulation of Wip1 and phosphorylated NF-κB p65 (p-p65). These retinal changes indicated retinal injury, characterized by increased TUNEL-positive RGCs, elevated cleaved caspase-3 levels, retinal thinning, and reduced electroretinography (ERG) amplitudes. Treatment with miR-16-5p mimics ameliorated these molecular, cellular, structural, and functional alterations, whereas miR‑16‑5p inhibitors exacerbated them. Collectively, miR-16-5p may protect RGCs from IR-induced apoptosis by suppressing astrocyte-mediated inflammation via the Wip1/NF-κB signaling axis.</p>

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miR‑16‑5p Protects RGCs Against Retinal Ischemia–Reperfusion Injury by Modulating Astrocyte-Mediated Neuroinflammation Through the Wip1/NF-κB Signaling Axis

  • 期刊论文

  • 发表日期：

    2026年1月1日

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  • Wen Hu,
  • Wenjing He,
  • Guangyi Huang,
  • Yuchen Zhou,
  • Yue Li,
  • Shuya Tao,
  • Daizai Lei,
  • Fen Tang,
  • Ningning Tang,
  • Li Jiang,
  • Qiangqiang Lan,
  • Hui Huang,
  • Qi Chen,
  • Shaoyang Zhang,
  • Hongran Fu,
  • Rong Huang,
  • Fan Xu

摘要

Astrocyte-mediated neuroinflammation has recently been implicated as a key contributor to neurodegeneration following retinal ischemia–reperfusion (IR) injury. However, the role of miR‑16‑5p in this process remains unclear. This study aimed to investigate the function and mechanism of miR‑16‑5p. TargetScan was used to predict miR-16-5p targets, which were validated by RNA pull-down. miR‑16‑5p expression was assessed by RT‑qPCR in IR retinas and in astrocytes after oxygen–glucose deprivation/reoxygenation (OGD/R). Astrocyte activation, inflammatory cytokine, and Wip1/nuclear factor kappa B (NF‑κB) signaling were examined following miR-16-5p modulation with mimics or inhibitors in vitro and in vivo. Retinal ganglion cell (RGC) apoptosis, retinal function, and morphology were evaluated. miR‑16‑5p was found to potentially target wild-type p53-induced phosphatase 1 (Wip1) and decreased Wip1 expression. In IR-injured mouse retinas and OGD/R-treated astrocytes, miR‑16‑5p expression was significantly downregulated. This decrease was accompanied by astrocyte activation, increased TNF-α and IL-1β levels, and upregulation of Wip1 and phosphorylated NF-κB p65 (p-p65). These retinal changes indicated retinal injury, characterized by increased TUNEL-positive RGCs, elevated cleaved caspase-3 levels, retinal thinning, and reduced electroretinography (ERG) amplitudes. Treatment with miR-16-5p mimics ameliorated these molecular, cellular, structural, and functional alterations, whereas miR‑16‑5p inhibitors exacerbated them. Collectively, miR-16-5p may protect RGCs from IR-induced apoptosis by suppressing astrocyte-mediated inflammation via the Wip1/NF-κB signaling axis.