AMPK Deficiency Induces Corneal Epithelial Barrier Dysfunction by Modulating Energy Homeostasis

This study aims to examine the impact of adenosine monophosphate-activated protein kinase (AMPK) on corneal epithelial barrier function and energy metabolism.

Corneal epithelial specific AMPK knockout mice were constructed to evaluate ocular surface phenotypes. In vitro experiments were performed using human corneal epithelial cells (HCECs) transfected with small interference RNA. Epithelial barrier function was assessed by analyzing apical junction complexes through immunofluorescence and Western blot in both in vivo and in vitro models. Changes in energy metabolism were evaluated by measuring oxygen consumption rate, mitochondrial dynamics protein expression, glucose uptake, and enzyme activity.

Increased corneal fluorescein sodium staining and irregularly shaped epithelial cells were observed in AMPK knockout mice. The staining patterns and protein levels of tight junction and adherens junction proteins, including ZO-1, occludin, and E-cadherin, were significantly impaired in the corneal epithelium of both knockout mice and AMPK knockdown HCECs. AMPK deficiency led to reduced oxidative phosphorylation, mitochondrial biogenesis, glucose uptake, and glycolysis in the corneal epithelium. Additionally, elevated inflammation was found in the corneal epithelium in the absence of AMPK.

This study suggests that energy metabolism disruption plays a pivotal role in corneal barrier dysfunction, and elucidates the metabolic and biological functions of AMPKα in the corneal epithelium, which may serve as a potential therapeutic target for ocular surface diseases associated with compromised barrier function.