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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2017-08-01
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doaj-8758b404d405418ca43ea07240fbe4ea2020-12-08T01:45:12ZengNature Publishing GroupScientific Reports2045-23222017-08-017111510.1038/s41598-017-07329-yROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathyPierre-Raphaël Rothschild0Sawsen Salah1Marianne Berdugo2Emmanuelle Gélizé3Kimberley Delaunay4Marie-Christine Naud5Christophe Klein6Alexandre Moulin7Michèle Savoldelli8Ciara Bergin9Jean-Claude Jeanny10Laurent Jonet11Yvan Arsenijevic12Francine Behar-Cohen13Patricia Crisanti14Inserm UMR_S 1138, Team 17: From physiopathology of retinal diseases to clinical advances, Centre de Recherche des CordeliersInserm UMR_S 1138, Team 17: From physiopathology of retinal diseases to clinical advances, Centre de Recherche des CordeliersInserm UMR_S 1138, Team 17: From physiopathology of retinal diseases to clinical advances, Centre de Recherche des CordeliersInserm UMR_S 1138, Team 17: From physiopathology of retinal diseases to clinical advances, Centre de Recherche des CordeliersInserm UMR_S 1138, Team 17: From physiopathology of retinal diseases to clinical advances, Centre de Recherche des CordeliersInserm UMR_S 1138, Team 17: From physiopathology of retinal diseases to clinical advances, Centre de Recherche des CordeliersInserm UMR_S 1138, Team 17: From physiopathology of retinal diseases to clinical advances, Centre de Recherche des CordeliersDepartment of Ophthalmology of University of Lausanne 1000 Lausanne, Jules Gonin HospitalInserm UMR_S 1138, Team 17: From physiopathology of retinal diseases to clinical advances, Centre de Recherche des CordeliersDepartment of Ophthalmology of University of Lausanne 1000 Lausanne, Jules Gonin HospitalInserm UMR_S 1138, Team 17: From physiopathology of retinal diseases to clinical advances, Centre de Recherche des CordeliersInserm UMR_S 1138, Team 17: From physiopathology of retinal diseases to clinical advances, Centre de Recherche des CordeliersDepartment of Ophthalmology of University of Lausanne 1000 Lausanne, Jules Gonin HospitalInserm UMR_S 1138, Team 17: From physiopathology of retinal diseases to clinical advances, Centre de Recherche des CordeliersInserm UMR_S 1138, Team 17: From physiopathology of retinal diseases to clinical advances, Centre de Recherche des CordeliersAbstract 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.https://doi.org/10.1038/s41598-017-07329-y |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-08-01 |
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. |
url |
https://doi.org/10.1038/s41598-017-07329-y |
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