Loss of Extracellular Signal-Regulated Kinase 1/2 in the Retinal Pigment Epithelium Leads to RPE65 Decrease and Retinal Degeneration

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Serval ID
serval:BIB_640E8CA325F7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Loss of Extracellular Signal-Regulated Kinase 1/2 in the Retinal Pigment Epithelium Leads to RPE65 Decrease and Retinal Degeneration
Journal
Molecular and Cellular Biology
Author(s)
Pyakurel Aswin, Balmer Delphine, Saba-El-Leil Marc, Kizilyaprak Caroline, Daraspe Jean, Humbel Bruno, Voisin Laure, Le Yun Z., von Lintig Johannes, Meloche Sylvain, Roduit Raphael
Publication state
Published
Issued date
28/11/2017
Peer-reviewed
Oui
Pages
NA
Language
english
Abstract
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.
Create date
03/10/2017 10:56
Last modification date
07/07/2021 6:35
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