<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Balmer, Delphine</dc:creator>
  <dc:creator>Bapst-Wicht, Linda</dc:creator>
  <dc:creator>Pyakurel, Aswin</dc:creator>
  <dc:creator>Emery, Martine</dc:creator>
  <dc:creator>Nanchen, Natacha</dc:creator>
  <dc:creator>Bochet, Christian G.</dc:creator>
  <dc:creator>Roduit, Raphael</dc:creator>
  <dc:date>2017</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">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.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://folia.unifr.ch/global/documents/305461</dc:identifier>
  <dc:identifier>https://folia.unifr.ch/documents/305461/files/boc_bra.pdf</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.3389/fnagi.2017.00043</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>License undefined</dc:rights>
  <dc:source>Frontiers in Aging Neuroscience. - 2017, vol. 9, p. 43</dc:source>
  <dc:subject>info:eu-repo/classification/udc/57</dc:subject>
  <dc:title xmlns:ns1="xml" ns1:lang="en">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</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>