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

被引：0

作者：

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

机构：

[1] Team 17: From physiopathology of retinal diseases to clinical advances,Inserm UMR_S 1138

[2] Centre de Recherche des Cordeliers,Sorbonne University

[3] University of Pierre et Marie Curie,Paris Descartes University

[4] UMR_S 1138,Department of Ophthalmology of University of Lausanne 1000 Lausanne

[5] Centre de Recherche des Cordeliers,Department of Ophthalmology

[6] Sorbonne Paris Cité,INSERM U1138 Team 17

[7] UMR_S 1138,undefined

[8] Centre de Recherche des Cordeliers,undefined

[9] Jules Gonin Hospital,undefined

[10] Assistance Publique-Hopitaux de Paris,undefined

[11] Hôtel-Dieu de Paris Hospital,undefined

[12] Le Centre de Recherches des Cordeliers (CRC),undefined

[13] University of Lausanne,undefined

来源：

Scientific Reports | / 7卷

关键词：

D O I：

暂无

中图分类号：

学科分类号：

摘要：

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.

引用

共 119 条

[41]

Shimokawa H(2013)Antiangiogenic properties of fasudil, a potent Rho-Kinase inhibitor J. Diabetes Metab. Disord. 12 60-698

[42]

Mishra RK(1999)Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans Am. J. Physiol. 277 C20-1561

[43]

Alokam R(2015)Peroxide-induced membrane blebbing in endothelial cells associated with glutathione oxidation but not apoptosis Circ. J. Off. J. Jpn. Circ. Soc. 79 934-3340

[44]

Sriram D(2001)Metabolic adaptations in diabetic endothelial cells Nat. Cell Biol. 3 339-24

[45]

Yogeeswari P(2015)Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I Mol. Vis. 21 688-75

[46]

Komers R(2008)Fasudil hydrochloride, a potent ROCK inhibitor, inhibits corneal neovascularization after alkali burns in mice Mol. Cancer Ther. 7 1551-2276

[47]

Guo R(2005)Fasudil-induced hypoxia-inducible factor-1alpha degradation disrupts a hypoxia-driven vascular endothelial growth factor autocrine mechanism in endothelial cells Invest. Ophthalmol. Vis. Sci. 46 3331-175

[48]

Arita R(2012)Nonlethal oxidant injury to human retinal pigment epithelium cells causes cell membrane blebbing but decreased MMP-2 activity PloS One 7 e32204-322

[49]

Kita T(2013)Matrix-bound PAI-1 supports cell blebbing via RhoA/ROCK1 signaling PloS One 8 e79150-undefined

[50]

Ahmadieh H(2007)PAI-1 -675 4G/5G polymorphism in association with diabetes and diabetic complications susceptibility: a meta-analysis study J. Cardiovasc. Pharmacol. 50 17-undefined

← 1 2 3 4 5 6 7 8 9 10 →