Ascorbic acid ameliorates corneal endothelial dysfunction and enhances cell proliferation via the noncanonical GLUT1-ERK axis

Yi Jen Hsueh, Yaa Jyuhn James Meir, Jui Yang Lai, Chieh Cheng Huang, Tsai Te Lu, David Hui Kang Ma, Chao Min Cheng, Wei Chi Wu, Hung Chi Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

8 Scopus citations

Abstract

Background: The pumping function of corneal endothelial cells (CECs) plays a pivotal role in the maintenance of corneal water homeostasis. Corneal endothelial dysfunction (CED) leads to corneal edema and opacity, but with the exception of keratoplasty, no optimal therapeutic strategies have been established for CED. In this study, we aimed to investigate the ameliorative effect of ascorbic acid (AA) on CED and the underlying mechanism of action in the corneal endothelium. Methods: Rabbit corneal endothelial damage was induced by anterior chamber injection of benzalkonium chloride (BAK). AA was topically administered to the corneal surface, and the transparency and thickness of the cornea were assessed by external eye photography, slit-lamp photography, and ultrasonic pachymetry. To further analyze the mechanism, rabbit CECs and immortalized human CECs (B4G12 cells) were cultured. A ferric reducing/antioxidant and AA (FRASC) assay was performed to measure the AA concentration. Cell proliferation was evaluated by cell counting and bromodeoxyuridine (BrdU) labeling assays, and protein expression was examined by liquid chromatography–mass spectrometry (LC/MS) and immunoblotting. The involvement of glucose transporter 1 (GLUT1) and phospho-ERK was evaluated via GLUT1-siRNA and phospho-ERK inhibitor (PD98059) treatment. Interpretation: We observed that topical AA ameliorates BAK-induced rabbit corneal endothelial damage. Furthermore, we demonstrated that AA is transported into B4G12 cells via GLUT1, and afterward, AA increases ERK phosphorylation and promotes cell proliferation. Our findings indicate that CEC proliferation stimulated via the noncanonical AA-GLUT1-ERK axis contributes to AA-enhanced healing of CED.

Original languageEnglish
Article number112306
JournalBiomedicine and Pharmacotherapy
Volume144
DOIs
StatePublished - 12 2021

Bibliographical note

Publisher Copyright:
© 2021

Keywords

  • Ascorbic acid
  • Corneal endothelial dysfunction (CED)
  • Glucose transporter 1 (GLUT1)
  • Noncanonical ERK pathway
  • Proliferation

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