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

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2017 Oct 18

PMID 29038159

Citations 8

Authors

Aswin Pyakurel

Delphine Balmer

Marc K Saba-El-Leil

Caroline Kizilyaprak

Jean Daraspe

Bruno M Humbel

Laure Voisin

Yun Z Le

Johannes von Lintig

Sylvain Meloche

Raphael Roduit

Affiliations

Soon will be listed here.

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 and 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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