Heliyon (Mar 2024)

BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade

  • Guangyi Huang,
  • Shaoyang Zhang,
  • Jing Liao,
  • Yuanjun Qin,
  • Yiyi Hong,
  • Qi Chen,
  • Yunru Lin,
  • Yue Li,
  • Lin Lan,
  • Wen Hu,
  • Kongqian Huang,
  • Fen Tang,
  • Ningning Tang,
  • Li Jiang,
  • Chaolan Shen,
  • Ling Cui,
  • Haibin Zhong,
  • Min Li,
  • Peng Lu,
  • Qinmeng Shu,
  • Yantao Wei,
  • Fan Xu

Journal volume & issue
Vol. 10, no. 5
p. e27114

Abstract

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Aims: Retinal ischemia/reperfusion (I/R) injury is implicated in the etiology of various ocular disorders. Prior research has demonstrated that bone marrow tyrosine kinase on chromosome X (BMX) contributes to the advancement of ischemic disease and inflammatory reactions. Consequently, the current investigation aims to evaluate BMX's impact on retinal I/R injury and clarify its implied mechanism of action. Main methods: This study utilized male and female systemic BMX knockout (BMX−/−) mice to conduct experiments. The utilization of Western blot assay and immunofluorescence labeling techniques was employed to investigate variations in the expression of protein and tissue localization. Histomorphological changes were observed through H&E staining and SD-OCT examination. Visual function changes were assessed through electrophysiological experiments. Furthermore, apoptosis in the retina was identified using the TUNEL assay, as well as the ELISA technique, which has been utilized to determine the inflammatory factors level. Key findings: Our investigation results revealed that the knockdown of BMX did not yield a significant effect on mouse retina. In mice, BMX knockdown mitigated the negative impact of I/R injury on retinal tissue structure and visual function. BMX knockdown effectively reduced apoptosis, suppressed inflammatory responses, and decreased inflammatory factors subsequent to I/R injury. The outcomes of the current investigation revealed that BMX knockdown partially protected the retina through downregulating phosphorylation of AKT/ERK/STAT3 pathway. Significance: Our investigation showed that BMX−/− reduces AKT, ERK, and STAT3 phosphorylation, reducing apoptosis and inflammation. Thus, this strategy protected the retina from structural and functional damage after I/R injury.

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