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R. Roduit, A. Dépond, D. F. Schorderet; Role of MAP Kinase Pathways in UV-Induced Retinal Pigment Epithelium Apoptosis. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2533.
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Retinal pigment epithelium (RPE) cells are constantly exposed to external injury which leads to their degeneration, dysfunction or loss. This may be responsible for several degenerative retinal diseases, including age-related macular degeneration (AMD). The MAPK (Mitogen-Activated Protein Kinases) constitute a major response element in signaling events by directly phosphorylating, and thereby modulating the activity of specific transcription factors. Recent studies have highlighted the key role of these pathways in numerous apoptotic processes. Overactivation of MAPK pathways have been associated with RPE cells death. UV radiation is part of sunlight spectrum and is divided into three wave bands (UV-A, UV-B and UV-C). UV irradiation can induce DNA damaged, which may result in programmed cell death (i.e. corneal epithelial cell apoptosis).
Human retinal pigment epithelial cells ARPE19 and enucleated mouse globes were exposed to 100J/m2 of UV-C. MAP Kinase pathways were studied by western blot analysis and luminescence assays to quantify phosphorylation of the kinases. Specific kinase inhibitors were used to analyze the signaling involved in RPE cells death.
The three major MAPK pathways (JNK, Erk and p38) are expressed in mouse RPE cells and ARPE19 cells. Experiments performed on ARPE19 cells showed that JNK1/2, as well as total p38 kinases were activated by short term exposure to UV-C. Exposure of whole enucleated eye to UV-C showed only an increase of JNK2 phosphorylation but not JNK1. Overactivation of those kinases by UV treatment lead to ARPE19 cells apoptosis. The use of specific inhibitors of JNK (JNKi peptide) and p38 (SB203580) decreased kinase activities, as well as UV-induced cell death.
These results argue in favor of an essential role of JNK and p38 in the apoptotic process induced by UV treatment. The use of specific kinase inhibitors may provide new tools to prevent RPE apoptosis specifically in RPE diseases.
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