AMPK Deficiency Induces Corneal Epithelial Barrier Dysfunction by Modulating Energy Homeostasis

Area of Science:

• Ophthalmology
• Cell Biology
• Metabolism

Background:

• Corneal epithelial barrier integrity is vital for ocular surface health.
• Energy metabolism plays a significant role in maintaining cellular functions.
• Adenosine monophosphate-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis.

Purpose of the Study:

• To investigate the role of AMPK in regulating corneal epithelial barrier function.
• To examine the impact of AMPK on corneal epithelial energy metabolism.
• To elucidate the therapeutic potential of targeting AMPK for ocular surface diseases.

Main Methods:

• Generated corneal epithelial specific AMPK knockout mice and utilized human corneal epithelial cells (HCECs) with AMPK knockdown.
• Assessed epithelial barrier function by analyzing tight junction and adherens junction proteins.
• Evaluated energy metabolism through oxygen consumption, mitochondrial dynamics, glucose uptake, and glycolysis assays.

Main Results:

• AMPK deficiency in corneal epithelium led to impaired barrier function, characterized by increased staining and disrupted junctional proteins.
• Knockout mice and HCECs showed compromised oxidative phosphorylation, mitochondrial biogenesis, glucose uptake, and glycolysis.
• Absence of AMPK resulted in elevated inflammation in the corneal epithelium.

Conclusions:

• Disruption of energy metabolism is a key factor in corneal barrier dysfunction.
• AMPK plays a critical role in maintaining corneal epithelial energy metabolism and barrier integrity.
• Targeting AMPK presents a potential therapeutic strategy for ocular surface diseases involving compromised barrier function.