ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy

Abstract In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated b...

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Autores principales:	Pierre-Raphaël Rothschild, Sawsen Salah, Marianne Berdugo, Emmanuelle Gélizé, Kimberley Delaunay, Marie-Christine Naud, Christophe Klein, Alexandre Moulin, Michèle Savoldelli, Ciara Bergin, Jean-Claude Jeanny, Laurent Jonet, Yvan Arsenijevic, Francine Behar-Cohen, Patricia Crisanti
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8758b404d405418ca43ea07240fbe4ea
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spelling	oai:doaj.org-article:8758b404d405418ca43ea07240fbe4ea2021-12-02T11:53:07ZROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy10.1038/s41598-017-07329-y2045-2322https://doaj.org/article/8758b404d405418ca43ea07240fbe4ea2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07329-yhttps://doaj.org/toc/2045-2322Abstract In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers. Activation of ROCK-1 induces focal vascular constrictions, endoluminal blebbing and subsequent retinal hypoxia. In RPE cells, actin cytoskeleton remodeling and membrane blebs in RPE cells contributes to outer barrier breakdown. Intraocular injection of fasudil, significantly reduces both retinal hypoxia and RPE barrier breakdown. Diabetes-induced cell blebbing may contribute to ischemic maculopathy and represent an intervention target.Pierre-Raphaël RothschildSawsen SalahMarianne BerdugoEmmanuelle GélizéKimberley DelaunayMarie-Christine NaudChristophe KleinAlexandre MoulinMichèle SavoldelliCiara BerginJean-Claude JeannyLaurent JonetYvan ArsenijevicFrancine Behar-CohenPatricia CrisantiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pierre-Raphaël Rothschild Sawsen Salah Marianne Berdugo Emmanuelle Gélizé Kimberley Delaunay Marie-Christine Naud Christophe Klein Alexandre Moulin Michèle Savoldelli Ciara Bergin Jean-Claude Jeanny Laurent Jonet Yvan Arsenijevic Francine Behar-Cohen Patricia Crisanti ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy
description	Abstract In diabetic retinopathy, the exact mechanisms leading to retinal capillary closure and to retinal barriers breakdown remain imperfectly understood. Rho-associated kinase (ROCK), an effector of the small GTPase Rho, involved in cytoskeleton dynamic regulation and cell polarity is activated by hyperglycemia. In one year-old Goto Kakizaki (GK) type 2 diabetic rats retina, ROCK-1 activation was assessed by its cellular distribution and by phosphorylation of its substrates, MYPT1 and MLC. In both GK rat and in human type 2 diabetic retinas, ROCK-1 is activated and associated with non-apoptotic membrane blebbing in retinal vessels and in retinal pigment epithelium (RPE) that respectively form the inner and the outer barriers. Activation of ROCK-1 induces focal vascular constrictions, endoluminal blebbing and subsequent retinal hypoxia. In RPE cells, actin cytoskeleton remodeling and membrane blebs in RPE cells contributes to outer barrier breakdown. Intraocular injection of fasudil, significantly reduces both retinal hypoxia and RPE barrier breakdown. Diabetes-induced cell blebbing may contribute to ischemic maculopathy and represent an intervention target.
format	article
author	Pierre-Raphaël Rothschild Sawsen Salah Marianne Berdugo Emmanuelle Gélizé Kimberley Delaunay Marie-Christine Naud Christophe Klein Alexandre Moulin Michèle Savoldelli Ciara Bergin Jean-Claude Jeanny Laurent Jonet Yvan Arsenijevic Francine Behar-Cohen Patricia Crisanti
author_facet	Pierre-Raphaël Rothschild Sawsen Salah Marianne Berdugo Emmanuelle Gélizé Kimberley Delaunay Marie-Christine Naud Christophe Klein Alexandre Moulin Michèle Savoldelli Ciara Bergin Jean-Claude Jeanny Laurent Jonet Yvan Arsenijevic Francine Behar-Cohen Patricia Crisanti
author_sort	Pierre-Raphaël Rothschild
title	ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy
title_short	ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy
title_full	ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy
title_fullStr	ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy
title_full_unstemmed	ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy
title_sort	rock-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: contribution to diabetic retinopathy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8758b404d405418ca43ea07240fbe4ea
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ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy

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