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Loss of Extracellular Signal-Regulated Kinase 1/2 in the Retinal Pigment Epithelium Leads to RPE65 Decrease and Retinal Degeneration.
Pyakurel, Aswin; Balmer, Delphine; Saba-El-Leil, Marc K; Kizilyaprak, Caroline; Daraspe, Jean; Humbel, Bruno M; Voisin, Laure; Le, Yun Z; von Lintig, Johannes; Meloche, Sylvain; Roduit, Raphaël.
Afiliación
  • Pyakurel A; Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland.
  • Balmer D; IRO, Institute for Research in Ophthalmology, Sion, Switzerland.
  • Saba-El-Leil MK; IRO, Institute for Research in Ophthalmology, Sion, Switzerland.
  • Kizilyaprak C; Institute for Research in Immunology and Cancer, Department of Pharmacology and Program of Molecular Biology, Université de Montréal, Montreal, Quebec, Canada.
  • Daraspe J; Electron Microscopy Facility, University of Lausanne, Lausanne, Switzerland.
  • Humbel BM; Electron Microscopy Facility, University of Lausanne, Lausanne, Switzerland.
  • Voisin L; Electron Microscopy Facility, University of Lausanne, Lausanne, Switzerland.
  • Le YZ; Institute for Research in Immunology and Cancer, Department of Pharmacology and Program of Molecular Biology, Université de Montréal, Montreal, Quebec, Canada.
  • von Lintig J; Department of Medicine Endocrinology and Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
  • Meloche S; Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
  • Roduit R; Institute for Research in Immunology and Cancer, Department of Pharmacology and Program of Molecular Biology, Université de Montréal, Montreal, Quebec, Canada.
Mol Cell Biol ; 37(24)2017 Dec 15.
Article en En | MEDLINE | ID: mdl-29038159
Recent work suggested that the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) is increased in the retinal pigment epithelium (RPE) of age-related macular degeneration (ARMD) patients and therefore could be an attractive therapeutic target. Notably, ERK1/2 pathway inhibitors are used in cancer therapy, with severe and noncharacterized ocular side effects. To decipher the role of ERK1/2 in RPE cells, we conditionally disrupted the Erk1 and Erk2 genes in mouse RPE. The loss of ERK1/2 activity resulted in a significant decrease in the level of RPE65 expression, a decrease in ocular retinoid levels concomitant with low visual function, and a rapid disorganization of RPE cells, ultimately leading to retinal degeneration. Our results identify the ERK1/2 pathway as a direct regulator of the visual cycle and a critical component of the viability of RPE and photoreceptor cells. Moreover, our results caution about the need for a very fine adjustment of kinase inhibition in cancer or ARMD treatment in order to avoid ocular side effects.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cis-trans-Isomerasas / Sistema de Señalización de MAP Quinasas / Epitelio Pigmentado de la Retina / Degeneración Macular Límite: Animals Idioma: En Revista: Mol Cell Biol Año: 2017 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cis-trans-Isomerasas / Sistema de Señalización de MAP Quinasas / Epitelio Pigmentado de la Retina / Degeneración Macular Límite: Animals Idioma: En Revista: Mol Cell Biol Año: 2017 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos