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Background <p>Mounting evidence indicates metabolic dysregulation in diabetic corneal neuropathy (DCN). This study elucidates how the chromatin remodeler Brahma-related gene 1 (BRG1) orchestrates glycolytic reprogramming to drive neurodegeneration and epithelial repair defects in DCN.</p> Methods <p>Type 1 diabetic mice were established via streptozotocin (STZ) injection. Glycolysis was inhibited using 2-deoxy-D-glucose (2-DG) to assess its role in DCN pathogenesis. BRG1 expression was modulated by subconjunctival plasmid delivery (overexpression/knockdown). Pathway screening identified BRG1 downstream effectors, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) inhibition (LY294002) confirmed regulatory hierarchy. Glycolytic flux was evaluated via Western blotting and immunofluorescence; corneal nerve integrity and epithelial healing were assessed by βIII-tubulin staining and sodium fluorescein assay.</p> Results <p>Hyperglycemia upregulated BRG1 and glycolytic enzymes in diabetic corneal nerves. BRG1 overexpression exacerbated epithelial repair delay and neurodegeneration, while knockdown partially reversed damage. BRG1 overexpression activated PI3K/AKT transcription, and PI3K/AKT inhibition did not alter BRG1 levels but rescued BRG1-induced pathologies.</p> Conclusions <p>Glycolytic reprogramming is a critical driver of DCN progression. BRG1 activates PI3K/AKT signaling to enhance glycolytic flux, thereby regulating DCN pathogenesis. Targeting this axis may offer novel therapeutic strategies.</p>

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BRG1 orchestrates diabetic corneal neuropathy via PI3K/AKT-mediated glycolytic reprogramming

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月1日

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  • Yuyang Deng,
  • Wenqu Chen,
  • Danling Liao,
  • Jianzhang Hu

摘要

Background

Mounting evidence indicates metabolic dysregulation in diabetic corneal neuropathy (DCN). This study elucidates how the chromatin remodeler Brahma-related gene 1 (BRG1) orchestrates glycolytic reprogramming to drive neurodegeneration and epithelial repair defects in DCN.

Methods

Type 1 diabetic mice were established via streptozotocin (STZ) injection. Glycolysis was inhibited using 2-deoxy-D-glucose (2-DG) to assess its role in DCN pathogenesis. BRG1 expression was modulated by subconjunctival plasmid delivery (overexpression/knockdown). Pathway screening identified BRG1 downstream effectors, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) inhibition (LY294002) confirmed regulatory hierarchy. Glycolytic flux was evaluated via Western blotting and immunofluorescence; corneal nerve integrity and epithelial healing were assessed by βIII-tubulin staining and sodium fluorescein assay.

Results

Hyperglycemia upregulated BRG1 and glycolytic enzymes in diabetic corneal nerves. BRG1 overexpression exacerbated epithelial repair delay and neurodegeneration, while knockdown partially reversed damage. BRG1 overexpression activated PI3K/AKT transcription, and PI3K/AKT inhibition did not alter BRG1 levels but rescued BRG1-induced pathologies.

Conclusions

Glycolytic reprogramming is a critical driver of DCN progression. BRG1 activates PI3K/AKT signaling to enhance glycolytic flux, thereby regulating DCN pathogenesis. Targeting this axis may offer novel therapeutic strategies.