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

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State: Public
Version: Final published version
Serval ID
serval:BIB_BE7FCF2F7BE8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy.
Journal
Scientific reports
Author(s)
Rothschild P.R., Salah S., Berdugo M., Gélizé E., Delaunay K., Naud M.C., Klein C., Moulin A., Savoldelli M., Bergin C., Jeanny J.C., Jonet L., Arsenijevic Y., Behar-Cohen F., Crisanti P.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
18/08/2017
Peer-reviewed
Oui
Volume
7
Number
1
Pages
8834
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Keywords
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology, Aged, Animals, Biomarkers, Case-Control Studies, Cytoskeleton/metabolism, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2/complications, Diabetic Retinopathy/etiology, Diabetic Retinopathy/metabolism, Diabetic Retinopathy/pathology, Disease Models, Animal, Endothelial Cells/drug effects, Endothelial Cells/metabolism, Endothelial Cells/ultrastructure, Female, Fluorescent Antibody Technique, Humans, Hypoxia/metabolism, Immunohistochemistry, Male, Middle Aged, Rats, Retinal Pigment Epithelium/drug effects, Retinal Pigment Epithelium/metabolism, Retinal Pigment Epithelium/pathology, Retinal Vessels/drug effects, Retinal Vessels/metabolism, Retinal Vessels/pathology, Retinal Vessels/ultrastructure, rho-Associated Kinases/genetics, rho-Associated Kinases/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
24/09/2017 19:01
Last modification date
20/08/2019 16:32
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