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Updated: Feb 2, 2026

Corneal Confocal Microscopy: A Novel Non-invasive Technique to Quantify Small Fibre Pathology in Peripheral Neuropathies
Published on: January 3, 2011
BRG1 orchestrates diabetic corneal neuropathy via PI3K/AKT-mediated glycolytic reprogramming
Yuyang Deng1, Wenqu Chen1, Danling Liao1
1Department of Ophthalmology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350005, China.
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.
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