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

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 est...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Corneal endothelial dysfunction (CED) Ascorbic acid Proliferation Glucose transporter 1 (GLUT1) Noncanonical ERK pathway Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/860bd248e2bb439eb40524ec6b9dbd49
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spelling	oai:doaj.org-article:860bd248e2bb439eb40524ec6b9dbd492021-11-14T04:29:26ZAscorbic acid ameliorates corneal endothelial dysfunction and enhances cell proliferation via the noncanonical GLUT1-ERK axis0753-332210.1016/j.biopha.2021.112306https://doaj.org/article/860bd248e2bb439eb40524ec6b9dbd492021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221010908https://doaj.org/toc/0753-3322Background: 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.Yi-Jen HsuehYaa-Jyuhn James MeirJui-Yang LaiChieh-Cheng HuangTsai-Te LuDavid Hui-Kang MaChao-Min ChengWei-Chi WuHung-Chi ChenElsevierarticleCorneal endothelial dysfunction (CED)Ascorbic acidProliferationGlucose transporter 1 (GLUT1)Noncanonical ERK pathwayTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112306- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Corneal endothelial dysfunction (CED) Ascorbic acid Proliferation Glucose transporter 1 (GLUT1) Noncanonical ERK pathway Therapeutics. Pharmacology RM1-950
spellingShingle	Corneal endothelial dysfunction (CED) Ascorbic acid Proliferation Glucose transporter 1 (GLUT1) Noncanonical ERK pathway Therapeutics. Pharmacology RM1-950 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 Ascorbic acid ameliorates corneal endothelial dysfunction and enhances cell proliferation via the noncanonical GLUT1-ERK axis
description	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.
format	article
author	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
author_facet	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
author_sort	Yi-Jen Hsueh
title	Ascorbic acid ameliorates corneal endothelial dysfunction and enhances cell proliferation via the noncanonical GLUT1-ERK axis
title_short	Ascorbic acid ameliorates corneal endothelial dysfunction and enhances cell proliferation via the noncanonical GLUT1-ERK axis
title_full	Ascorbic acid ameliorates corneal endothelial dysfunction and enhances cell proliferation via the noncanonical GLUT1-ERK axis
title_fullStr	Ascorbic acid ameliorates corneal endothelial dysfunction and enhances cell proliferation via the noncanonical GLUT1-ERK axis
title_full_unstemmed	Ascorbic acid ameliorates corneal endothelial dysfunction and enhances cell proliferation via the noncanonical GLUT1-ERK axis
title_sort	ascorbic acid ameliorates corneal endothelial dysfunction and enhances cell proliferation via the noncanonical glut1-erk axis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/860bd248e2bb439eb40524ec6b9dbd49
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Ascorbic acid ameliorates corneal endothelial dysfunction and enhances cell proliferation via the noncanonical GLUT1-ERK axis

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