ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy
| Autor: | Rothschild, Pierre-Raphaël, Salah, Sawsen, Berdugo, Marianne, Gelize, Emmanuelle, Delaunay, Kimberley, Naud, Marie-Christine, Klein, Christophe, Moulin, Alexandre, Savoldelli, Michèle, Bergin, Ciara, Jeanny, Jean-Claude, Jonet, Laurent, Arsenijevic, Yvan, Behar-Cohen, Francine, Crisanti, Patricia |
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| Přispěvatelé: | Assistance Publique-Hôpitaux de Paris, Department of Ophthalmology, Hôpital Cochin, Paris, France, Métabolisme et physiologie rénale (CRC - UMR_S 1138), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'opthalmologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Ophthalmology, Université de Lausanne (UNIL), Gérontologie, Institut National de la Santé et de la Recherche Médicale (INSERM), Développement, vieillissement et pathologie de la rétine, Unit of Retinal Degeneration and Regeneration, École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Hôtel-Dieu [Paris], Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École Pratique des Hautes Études (EPHE), Université de Lausanne = University of Lausanne (UNIL) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
[SDV]Life Sciences [q-bio] Science Fluorescent Antibody Technique Retinal Pigment Epithelium 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 Humans Hypoxia/metabolism Immunohistochemistry 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 Article 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Hypoxia ComputingMilieux_MISCELLANEOUS Cytoskeleton rho-Associated Kinases Diabetic Retinopathy Endothelial Cells Retinal Vessels eye diseases Diabetes Mellitus Type 2 Medicine sense organs |
| Zdroj: | Scientific reports, vol. 7, no. 1, pp. 8834 Scientific Reports, Vol 7, Iss 1, Pp 1-15 (2017) Scientific Reports Scientific Reports, Nature Publishing Group, 2017, 7 (1), ⟨10.1038/s41598-017-07329-y⟩ Scientific Reports, 2017, 7 (1), ⟨10.1038/s41598-017-07329-y⟩ |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-07329-y⟩ |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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