Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells

Abstract Corneal haze post refractive surgery is prevented by mitomycin c (MMC) treatment though it can lead to corneal endothelial damage, persistent epithelial defects and necrosis of cells. Suberanilohydroxamic acid (SAHA) however has been proposed to prevent corneal haze without any adverse effe...

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Autores principales:	Rohit Shetty, Nimisha Rajiv Kumar, Murali Subramani, Lekshmi Krishna, Ponnalagu Murugeswari, Himanshu Matalia, Pooja Khamar, Zelda V. Dadachanji, Rajiv R. Mohan, Arkasubhra Ghosh, Debashish Das
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e342de859592401f9fa932eecd3fc8a5
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spelling	oai:doaj.org-article:e342de859592401f9fa932eecd3fc8a52021-12-02T11:02:18ZSafety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells10.1038/s41598-021-83881-y2045-2322https://doaj.org/article/e342de859592401f9fa932eecd3fc8a52021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83881-yhttps://doaj.org/toc/2045-2322Abstract Corneal haze post refractive surgery is prevented by mitomycin c (MMC) treatment though it can lead to corneal endothelial damage, persistent epithelial defects and necrosis of cells. Suberanilohydroxamic acid (SAHA) however has been proposed to prevent corneal haze without any adverse effects. For clinical application we have investigated the short and long term outcome of cells exposed to SAHA. Human donor cornea, cultured limbal epithelial cells, corneal rims and lenticules were incubated with SAHA and MMC. The cells/tissue was then analyzed by RT-qPCR, immunofluorescence and western blot for markers of apoptosis and fibrosis. The results reveal that short term exposure of SAHA and SAHA + MMC reduced apoptosis levels and increased αSMA expression compared to those treated with MMC. Epithelial cells derived from cultured corneal rim that were incubated with the MMC, SAHA or MMC + SAHA revealed enhanced apoptosis, reduced levels of CK3/CK12, ∆NP63 and COL4A compared to other treatments. In SAHA treated lenticules TGFβ induced fibrosis was reduced. The results imply that MMC treatment for corneal haze has both short term and long term adverse effects on cells and the cellular properties. However, a combinatorial treatment of SAHA + MMC prevents expression of corneal fibrotic markers without causing any adverse effect on cellular properties.Rohit ShettyNimisha Rajiv KumarMurali SubramaniLekshmi KrishnaPonnalagu MurugeswariHimanshu MataliaPooja KhamarZelda V. DadachanjiRajiv R. MohanArkasubhra GhoshDebashish DasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rohit Shetty Nimisha Rajiv Kumar Murali Subramani Lekshmi Krishna Ponnalagu Murugeswari Himanshu Matalia Pooja Khamar Zelda V. Dadachanji Rajiv R. Mohan Arkasubhra Ghosh Debashish Das Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells
description	Abstract Corneal haze post refractive surgery is prevented by mitomycin c (MMC) treatment though it can lead to corneal endothelial damage, persistent epithelial defects and necrosis of cells. Suberanilohydroxamic acid (SAHA) however has been proposed to prevent corneal haze without any adverse effects. For clinical application we have investigated the short and long term outcome of cells exposed to SAHA. Human donor cornea, cultured limbal epithelial cells, corneal rims and lenticules were incubated with SAHA and MMC. The cells/tissue was then analyzed by RT-qPCR, immunofluorescence and western blot for markers of apoptosis and fibrosis. The results reveal that short term exposure of SAHA and SAHA + MMC reduced apoptosis levels and increased αSMA expression compared to those treated with MMC. Epithelial cells derived from cultured corneal rim that were incubated with the MMC, SAHA or MMC + SAHA revealed enhanced apoptosis, reduced levels of CK3/CK12, ∆NP63 and COL4A compared to other treatments. In SAHA treated lenticules TGFβ induced fibrosis was reduced. The results imply that MMC treatment for corneal haze has both short term and long term adverse effects on cells and the cellular properties. However, a combinatorial treatment of SAHA + MMC prevents expression of corneal fibrotic markers without causing any adverse effect on cellular properties.
format	article
author	Rohit Shetty Nimisha Rajiv Kumar Murali Subramani Lekshmi Krishna Ponnalagu Murugeswari Himanshu Matalia Pooja Khamar Zelda V. Dadachanji Rajiv R. Mohan Arkasubhra Ghosh Debashish Das
author_facet	Rohit Shetty Nimisha Rajiv Kumar Murali Subramani Lekshmi Krishna Ponnalagu Murugeswari Himanshu Matalia Pooja Khamar Zelda V. Dadachanji Rajiv R. Mohan Arkasubhra Ghosh Debashish Das
author_sort	Rohit Shetty
title	Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells
title_short	Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells
title_full	Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells
title_fullStr	Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells
title_full_unstemmed	Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells
title_sort	safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin c in reducing pro-fibrotic changes in human corneal epithelial cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e342de859592401f9fa932eecd3fc8a5
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Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells

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