# BRG1 Protein Drives Corneal Nerve Damage in Diabetic Mice via Glycolysis and PI3K/AKT

- Published: 2026-11-14 15:45 UTC
- Section: Life & Health › Medicine
- Tags: BRG1, diabetic corneal neuropathy, glycolytic reprogramming, PI3K/AKT signaling, corneal nerve degeneration, epithelial wound healing, streptozotocin mouse model, chromatin remodeler
- URL: https://realtech.media/news/rt-7dfc181afd7ae8e98cbf55de_brg1_protein_drives/

**In mice with streptozotocin-induced type 1 diabetes, the chromatin remodeler BRG1 activated PI3K/AKT and glycolysis, worsening corneal nerve loss and delaying epithelial healing.**

![BRG1 Protein Drives Corneal Nerve Damage in Diabetic Mice via Glycolysis and PI3K/AKT](https://realtech.media/media/2026/11/0d06d894a8e36d30.jpg)
*Ivan A. Novikov, Wikimedia Commons, CC BY-SA 4.0*

A mouse study published in Eye and Vision reports that the chromatin remodeler Brahma-related gene 1 (BRG1) drives diabetic corneal neuropathy by activating PI3K/AKT signaling and glycolytic reprogramming [1]. Type 1 diabetes was induced in male C57BL/6 mice with streptozotocin. Animals whose average blood glucose exceeded 350 milligrams per deciliter were classified as diabetic, and they also lost weight compared with controls.

Before this work, the upstream epigenetic mechanism behind the metabolic shift in diabetic corneal nerves had not been resolved. BRG1 is the catalytic ATPase subunit of the SWI/SNF chromatin remodeling complex. In cancer studies, its deficiency suppressed glycolysis and reduced glucose consumption. Its role in diabetic corneal neuropathy had not been examined.

## Experimental design and measurements

The authors inhibited glycolysis with 2-deoxy-D-glucose (2-DG) to test its role in the disease. BRG1 was overexpressed or knocked down by subconjunctival plasmid delivery. The PI3K/AKT inhibitor LY294002 was used to establish the order of regulation between the two factors.

Corneal sensitivity was measured in awake animals with a Cochet-Bonnet aesthesiometer. Epithelial healing was assessed after a standardized central epithelial defect of 2.5 millimeters, stained with sodium fluorescein and imaged under cobalt blue light. Nerve integrity was evaluated by βIII-tubulin staining. Glycolytic flux was examined by Western blotting and immunofluorescence [1].

## Results in diabetic mice

Hyperglycemia raised the levels of BRG1 and glycolytic enzymes in diabetic corneal nerves, according to the authors [1]. In diabetic animals this was accompanied by corneal nerve degeneration, reduced sensory responsiveness and slower closure of the epithelial wound.

BRG1 overexpression worsened the delay in epithelial repair and the neurodegeneration. Knockdown partially reversed the damage. BRG1 overexpression activated PI3K/AKT transcription. Inhibiting PI3K/AKT did not change BRG1 levels, but it rescued the pathologies induced by BRG1 [1].

The authors conclude that BRG1 activates PI3K/AKT signaling to increase glycolytic flux, and that glycolytic reprogramming is a critical driver of diabetic corneal neuropathy progression. They state that targeting this axis may offer new therapeutic strategies. The results come from a mouse model.

## Sources

1. [Eye and Vision](https://doi.org/10.1186/s40662-026-00474-4)
2. [bioengineer.org](https://bioengineer.org/brg1-protein-drives-diabetic-corneal-nerve-damage-through-glycolytic-reprogramming-in-mice)

---

Source: RealTech, realtech.media — https://realtech.media/news/rt-7dfc181afd7ae8e98cbf55de_brg1_protein_drives/