serval:BIB_BE7FCF2F7BE8
ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy.
10.1038/s41598-017-07329-y
000407980000088
28821742
Rothschild
P.R.
author
Salah
S.
author
Berdugo
M.
author
Gélizé
E.
author
Delaunay
K.
author
Naud
M.C.
author
Klein
C.
author
Moulin
A.
author
Savoldelli
M.
author
Bergin
C.
author
Jeanny
J.C.
author
Jonet
L.
author
Arsenijevic
Y.
author
Behar-Cohen
F.
author
Crisanti
P.
author
article
2017-08-18
Scientific reports
2045-2322
2045-2322
journal
7
1
8834
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.
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
eng
60_published
true
peer-reviewed
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
University of Lausanne
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