Related Experiment Video
Updated: Apr 11, 2026
Ex Vivo Corneal Organ Culture Model for Wound Healing Studies
Published on: February 15, 2019
PFKFB3 functions as a metabolic checkpoint in corneal fibrosis by coordinating glycolytic reprogramming, fibrotic
ShuMei Yang1, XinLin Yan2, YaPeng Jing3
1Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin, China.
Aims:
Corneal fibrosis is a leading cause of blindness with limited treatment options. This study explores the role of PFKFB3-driven glycolytic reprogramming in the development of corneal fibrosis and evaluates its potential as a therapeutic target.
Materials And Methods:
An alkali burn-induced corneal injury model was established in C57BL/6 mice to investigate temporal changes in glycolysis during wound healing. Pathological alterations were assessed using slit-lamp microscopy, hematoxylin and eosin (H&E) staining, proteomic analysis, and Western blotting. Glycolytic flux was measured by determining the extracellular acidification rate (ECAR) in both injured corneas and cultured keratocytes stimulated with TGF-β1 or LPS. Further mechanistic studies were conducted to elucidate the specific role of PFKFB3 in corneal repair.
Key Findings:
Proteomic analysis revealed a significant enrichment of glycolytic pathways during corneal repair. Following alkali injury, murine corneas exhibited a time-dependent increase in glycolytic activity, peaking at day 14, coinciding with the fibrotic phase of wound healing. Pharmacological inhibition of PFKFB3 in vivo produced multiple therapeutic benefits, including accelerated wound closure, reduced corneal opacity, and suppressed myofibroblast differentiation. This intervention also decreased the ECAR and reduced the production of fibrotic extracellular matrix components. Complementary in vitro studies confirmed that PFKFB3 blockade effectively mitigated both TGF-β1-induced fibrotic transformation and LPS-mediated inflammatory activation in keratocytes.
Significance:
In conclusion, our study identifies PFKFB3-driven glycolytic reprogramming as a critical metabolic checkpoint in corneal fibrosis. Targeting this node pathway attenuates both myofibroblast transformation and inflammatory responses.
Insights
Targeting 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) can treat corneal fibrosis. This study shows PFKFB3 inhibition reduces opacity and myofibroblast differentiation, offering a new therapeutic strategy for vision impairment.
Area of Science:
- Ophthalmology
- Metabolic pathways
- Cellular biology
Background:
- Corneal fibrosis is a significant cause of blindness with limited therapeutic options.
- Glycolytic reprogramming plays a role in the pathogenesis of corneal fibrosis.
Purpose of the Study:
- To investigate the role of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3)-driven glycolytic reprogramming in corneal fibrosis.
- To evaluate PFKFB3 as a potential therapeutic target for corneal fibrosis.
Main Methods:
- Established an alkali burn-induced corneal injury model in mice.
- Assessed pathological changes using slit-lamp microscopy, H&E staining, proteomics, and Western blotting.
- Measured glycolytic flux via extracellular acidification rate (ECAR) and investigated PFKFB3's role in vitro and in vivo.
Main Results:
- Corneal repair showed increased glycolytic pathway enrichment and activity, peaking during the fibrotic phase.
- Inhibition of PFKFB3 accelerated wound healing, reduced corneal opacity, and suppressed myofibroblast differentiation.
- PFKFB3 blockade decreased ECAR, reduced extracellular matrix production, and mitigated TGF-β1-induced fibrosis and LPS-induced inflammation in keratocytes.
Conclusions:
- PFKFB3-driven glycolytic reprogramming is a critical metabolic checkpoint in corneal fibrosis.
- Targeting PFKFB3 effectively attenuates both myofibroblast transformation and inflammatory responses in the cornea.
- PFKFB3 inhibition presents a promising therapeutic strategy for corneal fibrosis and vision restoration.
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