Deciphering the mechanoresponsive role of β-catenin in keratoconus epithelium

Abstract Keratoconus (KC) is a corneal dystrophy characterized by progressive ectasia that leads to severe visual impairment and remains one of the leading indications for corneal transplantation. The etiology is believed to be multifactorial and alterations have been documented in the biomechanical...

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Autores principales:	Chatterjee Amit, Prema Padmanabhan, Janakiraman Narayanan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/be48bfa4650746e784ac654ca84c0346
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spelling	oai:doaj.org-article:be48bfa4650746e784ac654ca84c03462021-12-02T15:10:30ZDeciphering the mechanoresponsive role of β-catenin in keratoconus epithelium10.1038/s41598-020-77138-32045-2322https://doaj.org/article/be48bfa4650746e784ac654ca84c03462020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77138-3https://doaj.org/toc/2045-2322Abstract Keratoconus (KC) is a corneal dystrophy characterized by progressive ectasia that leads to severe visual impairment and remains one of the leading indications for corneal transplantation. The etiology is believed to be multifactorial and alterations have been documented in the biomechanical, biochemical and ultrastructural characteristics of the cornea. While the exact site of disease origin is still debated, changes in the corneal epithelium are believed to occur even before the disease is clinically manifested. In this study we investigate the possible role of β-catenin as mechanotransducer in KC corneal epithelium. The sheets of corneal epithelium removed from keratoconic eyes when they underwent collagen crosslinking as a therapeutic procedure were used for this study. The healthy corneal epithelium of patients undergoing Laser Refractive Surgery for the correction of their refractive error, served as controls. Immunoblotting and tissue immunofluorescence studies were performed on KC epithelium to analyse the expression and localization of β-catenin, E-cadherin, ZO1, α-catenin, Cyclin D1, α-actinin, RhoA, and Rac123. Co-immunoprecipitation of β-catenin followed by mass spectrometry of KC epithelium was performed to identify its interacting partners. This was further validated by using epithelial tissues grown on scaffolds of different stiffness. Histology data reported breaks in the Bowman’s layer in KC patients. We hypothesize that these breaks expose the epithelium to the keratoconic corneal stroma, which, is known to have a decreased elastic modulus and that β-catenin acts as a mechanotransducer that induces structural changes such as loss of polarity (Syntaxin3) and barrier function (ZO1) through membrane delocalization. The results of our study strongly suggest that β-catenin could be a putative mechanotransducer in KC epithelium, thus supporting our hypothesis.Chatterjee AmitPrema PadmanabhanJanakiraman NarayananNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chatterjee Amit Prema Padmanabhan Janakiraman Narayanan Deciphering the mechanoresponsive role of β-catenin in keratoconus epithelium
description	Abstract Keratoconus (KC) is a corneal dystrophy characterized by progressive ectasia that leads to severe visual impairment and remains one of the leading indications for corneal transplantation. The etiology is believed to be multifactorial and alterations have been documented in the biomechanical, biochemical and ultrastructural characteristics of the cornea. While the exact site of disease origin is still debated, changes in the corneal epithelium are believed to occur even before the disease is clinically manifested. In this study we investigate the possible role of β-catenin as mechanotransducer in KC corneal epithelium. The sheets of corneal epithelium removed from keratoconic eyes when they underwent collagen crosslinking as a therapeutic procedure were used for this study. The healthy corneal epithelium of patients undergoing Laser Refractive Surgery for the correction of their refractive error, served as controls. Immunoblotting and tissue immunofluorescence studies were performed on KC epithelium to analyse the expression and localization of β-catenin, E-cadherin, ZO1, α-catenin, Cyclin D1, α-actinin, RhoA, and Rac123. Co-immunoprecipitation of β-catenin followed by mass spectrometry of KC epithelium was performed to identify its interacting partners. This was further validated by using epithelial tissues grown on scaffolds of different stiffness. Histology data reported breaks in the Bowman’s layer in KC patients. We hypothesize that these breaks expose the epithelium to the keratoconic corneal stroma, which, is known to have a decreased elastic modulus and that β-catenin acts as a mechanotransducer that induces structural changes such as loss of polarity (Syntaxin3) and barrier function (ZO1) through membrane delocalization. The results of our study strongly suggest that β-catenin could be a putative mechanotransducer in KC epithelium, thus supporting our hypothesis.
format	article
author	Chatterjee Amit Prema Padmanabhan Janakiraman Narayanan
author_facet	Chatterjee Amit Prema Padmanabhan Janakiraman Narayanan
author_sort	Chatterjee Amit
title	Deciphering the mechanoresponsive role of β-catenin in keratoconus epithelium
title_short	Deciphering the mechanoresponsive role of β-catenin in keratoconus epithelium
title_full	Deciphering the mechanoresponsive role of β-catenin in keratoconus epithelium
title_fullStr	Deciphering the mechanoresponsive role of β-catenin in keratoconus epithelium
title_full_unstemmed	Deciphering the mechanoresponsive role of β-catenin in keratoconus epithelium
title_sort	deciphering the mechanoresponsive role of β-catenin in keratoconus epithelium
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/be48bfa4650746e784ac654ca84c0346
work_keys_str_mv	AT chatterjeeamit decipheringthemechanoresponsiveroleofbcatenininkeratoconusepithelium AT premapadmanabhan decipheringthemechanoresponsiveroleofbcatenininkeratoconusepithelium AT janakiramannarayanan decipheringthemechanoresponsiveroleofbcatenininkeratoconusepithelium
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Deciphering the mechanoresponsive role of β-catenin in keratoconus epithelium

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