Prednisolone induces apoptosis in corneal epithelial cells through the intrinsic pathway

Abstract Glucocorticoid eye drops are one of the most widely used medications in ophthalmology. However, little is known about the effects of glucocorticoids on corneal epithelial cells that are directly exposed to topically-administered glucocorticoids. Here we investigated the effects of prednisol...

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Autores principales:	Jin Suk Ryu, Jung Hwa Ko, Mee Kum Kim, Won Ryang Wee, Joo Youn Oh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c59afde3325047f9b9a0fcea78480118
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spelling	oai:doaj.org-article:c59afde3325047f9b9a0fcea784801182021-12-02T16:05:59ZPrednisolone induces apoptosis in corneal epithelial cells through the intrinsic pathway10.1038/s41598-017-04509-82045-2322https://doaj.org/article/c59afde3325047f9b9a0fcea784801182017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04509-8https://doaj.org/toc/2045-2322Abstract Glucocorticoid eye drops are one of the most widely used medications in ophthalmology. However, little is known about the effects of glucocorticoids on corneal epithelial cells that are directly exposed to topically-administered glucocorticoids. Here we investigated the effects of prednisolone, a synthetic glucocorticoid analogue frequently used in the clinic, on corneal epithelial cells. Results showed that prednisolone decreased survival of corneal epithelial cells by inhibiting proliferation and inducing apoptosis in a dose-dependent manner. The levels of mitochondrial reactive oxygen species (mtROS), cleaved caspase-3, and -9 were increased by prednisolone. The effects of prednisolone on apoptosis and mtROS were blocked 1) by the glucocorticoid receptor (GR) antagonist RU-38486, 2) in cells with GR siRNA knockdown, and 3) by treatment with N-acetylcysteine. Transcript levels of pro-inflammatory cytokines were increased in corneal epithelial cells upon hyperosmolar stress, but repressed by prednisolone. In NOD.B10.H2b mice, topical administration of 1% prednisolone increased apoptotic cells in the corneal epithelium. Together, data indicate that prednisolone induces apoptosis in corneal epithelial cells through GR and the intrinsic pathway involving mtROS, caspase-9, and -3. The pro-apoptotic effects of glucocorticoids along with their anti-inflammatory effects should be considered when glucocorticoid eye drops are used in patients with ocular surface disease.Jin Suk RyuJung Hwa KoMee Kum KimWon Ryang WeeJoo Youn OhNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jin Suk Ryu Jung Hwa Ko Mee Kum Kim Won Ryang Wee Joo Youn Oh Prednisolone induces apoptosis in corneal epithelial cells through the intrinsic pathway
description	Abstract Glucocorticoid eye drops are one of the most widely used medications in ophthalmology. However, little is known about the effects of glucocorticoids on corneal epithelial cells that are directly exposed to topically-administered glucocorticoids. Here we investigated the effects of prednisolone, a synthetic glucocorticoid analogue frequently used in the clinic, on corneal epithelial cells. Results showed that prednisolone decreased survival of corneal epithelial cells by inhibiting proliferation and inducing apoptosis in a dose-dependent manner. The levels of mitochondrial reactive oxygen species (mtROS), cleaved caspase-3, and -9 were increased by prednisolone. The effects of prednisolone on apoptosis and mtROS were blocked 1) by the glucocorticoid receptor (GR) antagonist RU-38486, 2) in cells with GR siRNA knockdown, and 3) by treatment with N-acetylcysteine. Transcript levels of pro-inflammatory cytokines were increased in corneal epithelial cells upon hyperosmolar stress, but repressed by prednisolone. In NOD.B10.H2b mice, topical administration of 1% prednisolone increased apoptotic cells in the corneal epithelium. Together, data indicate that prednisolone induces apoptosis in corneal epithelial cells through GR and the intrinsic pathway involving mtROS, caspase-9, and -3. The pro-apoptotic effects of glucocorticoids along with their anti-inflammatory effects should be considered when glucocorticoid eye drops are used in patients with ocular surface disease.
format	article
author	Jin Suk Ryu Jung Hwa Ko Mee Kum Kim Won Ryang Wee Joo Youn Oh
author_facet	Jin Suk Ryu Jung Hwa Ko Mee Kum Kim Won Ryang Wee Joo Youn Oh
author_sort	Jin Suk Ryu
title	Prednisolone induces apoptosis in corneal epithelial cells through the intrinsic pathway
title_short	Prednisolone induces apoptosis in corneal epithelial cells through the intrinsic pathway
title_full	Prednisolone induces apoptosis in corneal epithelial cells through the intrinsic pathway
title_fullStr	Prednisolone induces apoptosis in corneal epithelial cells through the intrinsic pathway
title_full_unstemmed	Prednisolone induces apoptosis in corneal epithelial cells through the intrinsic pathway
title_sort	prednisolone induces apoptosis in corneal epithelial cells through the intrinsic pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c59afde3325047f9b9a0fcea78480118
work_keys_str_mv	AT jinsukryu prednisoloneinducesapoptosisincornealepithelialcellsthroughtheintrinsicpathway AT junghwako prednisoloneinducesapoptosisincornealepithelialcellsthroughtheintrinsicpathway AT meekumkim prednisoloneinducesapoptosisincornealepithelialcellsthroughtheintrinsicpathway AT wonryangwee prednisoloneinducesapoptosisincornealepithelialcellsthroughtheintrinsicpathway AT jooyounoh prednisoloneinducesapoptosisincornealepithelialcellsthroughtheintrinsicpathway
_version_	1718385174723428352

Prednisolone induces apoptosis in corneal epithelial cells through the intrinsic pathway

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