Bis-retinoid A2E induces an increase of basic fibroblast growth factor via inhibition of extracellular signal-regulated kinases 1/2 pathway in retinal pigment epithelium cells and facilitates phagocytosis
- Balmer, Delphine Institute for Research in Ophthalmology, Sion, Switzerland
- Bapst-Wicht, Linda Institute for Research in Ophthalmology, Sion, Switzerland
- Pyakurel, Aswin Institute for Research in Ophthalmology, Sion, Switzerland - Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland
- Emery, Martine Institute for Research in Ophthalmology, Sion, Switzerland
- Nanchen, Natacha Institute for Research in Ophthalmology, Sion, Switzerland
- Bochet, Christian G. Department of Chemistry, University of Fribourg, Switzerland
- Roduit, Raphael Institute for Research in Ophthalmology, Sion, Switzerland - Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, Lausanne, Switzerland
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2017
Published in:
- Frontiers in Aging Neuroscience. - 2017, vol. 9, p. 43
English
Age-related macular degeneration (ARMD) is the leading cause of vision loss in developed countries. Hallmarks of the disease are well known; indeed, this pathology is characterized by lipofuscin accumulation, is principally composed of lipid-containing residues of lysosomal digestion. The N-retinyl-N-retinylidene ethanolamine (A2E) retinoid which is thought to be a cytotoxic component for RPE is the best- characterized component of lipofuscin so far. Even if no direct correlation between A2E spatial distribution and lipofuscin fluorescence has been established in aged human RPE, modified forms or metabolites of A2E could be involved in ARMD pathology. Mitogen-activated protein kinase (MAPK) pathways have been involved in many pathologies, but not in ARMD. Therefore, we wanted to analyze the effects of A2E on MAPKs in polarized ARPE19 and isolated mouse RPE cells. We showed that long-term exposure of polarized ARPE19 cells to low A2E dose induces a strong decrease of the extracellular signal-regulated kinases' (ERK1/2) activity. In addition, we showed that A2E, via ERK1/2 decrease, induces a significant decrease of the retinal pigment epithelium-specific protein 65 kDa (RPE65) expression in ARPE19 cells and isolated mouse RPE. In the meantime, we showed that the decrease of ERK1/2 activity mediates an increase of basic fibroblast growth factor (bFGF) mRNA expression and secretion that induces an increase in phagocytosis via a paracrine effect. We suggest that the accumulation of deposits coming from outer segments (OS) could be explained by both an increase of bFGF-induced phagocytosis and by the decrease of clearance by A2E. The bFGF angiogenic protein may therefore be an attractive target to treat ARMD.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Chimie
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 288573
- DOI 10.3389/fnagi.2017.00043
- Persistent URL
- https://folia.unifr.ch/unifr/documents/305461
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