β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells

Abstract Background Topical application of β-blocker eye drops induces damage to the ocular surface in clinical. However, the mechanism involved remains incompletely understood. The purpose of this study was to investigate the influence and mechanism of β-blocker eye drops on corneal epithelial woun...

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Autores principales:	Xingyue Yuan, Xiubin Ma, Lingling Yang, Qingjun Zhou, Ya Li
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	β-Blocker eye drops β2-adrenoceptor Corneal Limbal stem cells Wound healing Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/dff98288305348b083912c9ef8e94a88
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spelling	oai:doaj.org-article:dff98288305348b083912c9ef8e94a882021-12-05T12:26:36Zβ-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells10.1186/s12886-021-02186-w1471-2415https://doaj.org/article/dff98288305348b083912c9ef8e94a882021-12-01T00:00:00Zhttps://doi.org/10.1186/s12886-021-02186-whttps://doaj.org/toc/1471-2415Abstract Background Topical application of β-blocker eye drops induces damage to the ocular surface in clinical. However, the mechanism involved remains incompletely understood. The purpose of this study was to investigate the influence and mechanism of β-blocker eye drops on corneal epithelial wound healing. Methods Corneal epithelial wound healing models were constructed by epithelial scraping including in the limbal region and unceasingly received eye drops containing 5 mg/mL β-blocker levobunolol, β1-adrenoceptor (β1AR)-specific antagonist atenolol or β2-adrenoceptor (β2AR)-specific antagonist ICI 118, 551. For the migration assay, the murine corneal epithelial stem/progenitor cells (TKE2) were wounded and subsequently incubated with levobunolol, atenolol, or ICI 118, 551. The proliferation and colony formation abilities of TKE2 cells treated with levobunolol, atenolol, or ICI 118, 551 were investigated by CCK-8 kit and crystal violet staining. The differentiation marker Cytokeratin 3 (CK3), the stem cell markers-Cytokeratin 14 (CK14) and Cytokeratin 19 (CK19), and corneal epithelium regeneration-related signaling including in Ki67 and the phosphorylated epithelial growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) were assessed by immunofluorescence staining. Results Levobunolol and ICI 118, 551 impaired corneal wound healing, decreased the expressions of CK3, CK14, and CK19 after limbal region scraping in vivo and reduced the migration and proliferation of TKE2 in vitro, whereas atenolol had no significant effect. Moreover, levobunolol and ICI 118, 551 inhibited corneal wound healing by mediating the expression of Ki67, and the phosphorylation of EGFR and ERK1/2 in the limbal and regenerated corneal epithelium. Conclusion β-blocker eye drops impaired corneal wound healing by inhibiting the β2AR of limbal stem cells, which decreased corneal epithelial regeneration-related signaling. Therefore, a selective β1AR antagonist might be a good choice for glaucoma treatment to avoid ocular surface damage.Xingyue YuanXiubin MaLingling YangQingjun ZhouYa LiBMCarticleβ-Blocker eye dropsβ2-adrenoceptorCornealLimbal stem cellsWound healingOphthalmologyRE1-994ENBMC Ophthalmology, Vol 21, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	β-Blocker eye drops β2-adrenoceptor Corneal Limbal stem cells Wound healing Ophthalmology RE1-994
spellingShingle	β-Blocker eye drops β2-adrenoceptor Corneal Limbal stem cells Wound healing Ophthalmology RE1-994 Xingyue Yuan Xiubin Ma Lingling Yang Qingjun Zhou Ya Li β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells
description	Abstract Background Topical application of β-blocker eye drops induces damage to the ocular surface in clinical. However, the mechanism involved remains incompletely understood. The purpose of this study was to investigate the influence and mechanism of β-blocker eye drops on corneal epithelial wound healing. Methods Corneal epithelial wound healing models were constructed by epithelial scraping including in the limbal region and unceasingly received eye drops containing 5 mg/mL β-blocker levobunolol, β1-adrenoceptor (β1AR)-specific antagonist atenolol or β2-adrenoceptor (β2AR)-specific antagonist ICI 118, 551. For the migration assay, the murine corneal epithelial stem/progenitor cells (TKE2) were wounded and subsequently incubated with levobunolol, atenolol, or ICI 118, 551. The proliferation and colony formation abilities of TKE2 cells treated with levobunolol, atenolol, or ICI 118, 551 were investigated by CCK-8 kit and crystal violet staining. The differentiation marker Cytokeratin 3 (CK3), the stem cell markers-Cytokeratin 14 (CK14) and Cytokeratin 19 (CK19), and corneal epithelium regeneration-related signaling including in Ki67 and the phosphorylated epithelial growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) were assessed by immunofluorescence staining. Results Levobunolol and ICI 118, 551 impaired corneal wound healing, decreased the expressions of CK3, CK14, and CK19 after limbal region scraping in vivo and reduced the migration and proliferation of TKE2 in vitro, whereas atenolol had no significant effect. Moreover, levobunolol and ICI 118, 551 inhibited corneal wound healing by mediating the expression of Ki67, and the phosphorylation of EGFR and ERK1/2 in the limbal and regenerated corneal epithelium. Conclusion β-blocker eye drops impaired corneal wound healing by inhibiting the β2AR of limbal stem cells, which decreased corneal epithelial regeneration-related signaling. Therefore, a selective β1AR antagonist might be a good choice for glaucoma treatment to avoid ocular surface damage.
format	article
author	Xingyue Yuan Xiubin Ma Lingling Yang Qingjun Zhou Ya Li
author_facet	Xingyue Yuan Xiubin Ma Lingling Yang Qingjun Zhou Ya Li
author_sort	Xingyue Yuan
title	β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells
title_short	β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells
title_full	β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells
title_fullStr	β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells
title_full_unstemmed	β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells
title_sort	β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells
publisher	BMC
publishDate	2021
url	https://doaj.org/article/dff98288305348b083912c9ef8e94a88
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β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells

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