title: Triamcinolone regulated apopto-phagocytic gene expression patterns in the clearance of dying retinal pigment epithelial cells. A key role of Mertk in the enhanced phagocytosis.
abstract: BACKGROUND
  The apopto-phagocytic gene expression patterns during clearance of dying cells in the retina and the effect of triamcinolone (TC) upon these processes have relevance to development of age-related macular degeneration (AMD).
  
  
  METHODS
  ARPE-19 cells and primary human retinal pigment epithelium (hRPE) were induced to undergo cell death by anoikis and the clearance of these cells by living hRPE/ARPE-19 or human monocyte-derived macrophages (HMDMs) in the presence or absence of TC was quantified by flow cytometry. TaqMan low-density gene expression array determining known markers of phagocytosis and loss-of-function studies on selected apopto-phagocytic genes was carried out in HMDM engulfing anoikic cells.
  
  
  RESULTS
  The glucocorticoid TC had a profound phagocytosis-enhancing effect on HMDM engulfing anoikic ARPE-19 or hRPE cells, causing a selective upregulation of the Mer tyrosine kinase (MERTK) receptor, while decreasing the expression of the AXL receptor tyrosine kinase and thrombospondin-1 (THSB-1). The key role of the MERTK could be demonstrated in HMDM engulfing dying cells using gene silencing as well as blocking antibodies. Similar pathways were found upregulated in living ARPE-19 engulfing anoikic ARPE-19 cells. Gas6 treatment enhanced phagocytosis in TC-treated HMDMs.
  
  
  CONCLUSIONS
  Specific agonists of the Mertk receptor may have a potential role as phagocytosis enhancers in the retina and serve as future targets for AMD therapy.
  
  
  CONCLUSIONS
  The use of Gas6 as enhancer of retinal phagocytosis via the MerTK receptor, alone or in combination with other specific ligands of the tyrosine kinase receptors' family may have a potential role in AMD therapy.
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary; Stem Cells and Eye Research Laboratory, Department of Biochemistry and Molecular Biology, and MTA-DE Stem cell, Apoptosis and Genomics Research Group, University of Debrecen, Debrecen, Hungary.
authors.forename: Réka
authors.initials: R
authors.lastname: Albert
authors.affiliation: Stem Cells and Eye Research Laboratory, Department of Biochemistry and Molecular Biology, and MTA-DE Stem cell, Apoptosis and Genomics Research Group, University of Debrecen, Debrecen, Hungary.
authors.forename: Endre
authors.initials: E
authors.lastname: Kristóf
authors.affiliation: UD Genomed Ltd., Debrecen, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Zahuczky
authors.affiliation: Stem Cells and Eye Research Laboratory, Department of Biochemistry and Molecular Biology, and MTA-DE Stem cell, Apoptosis and Genomics Research Group, University of Debrecen, Debrecen, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Szatmári-Tóth
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary; Stem Cells and Eye Research Laboratory, Department of Biochemistry and Molecular Biology, and MTA-DE Stem cell, Apoptosis and Genomics Research Group, University of Debrecen, Debrecen, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Veréb
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary; Stem Cells and Eye Research Laboratory, Department of Biochemistry and Molecular Biology, and MTA-DE Stem cell, Apoptosis and Genomics Research Group, University of Debrecen, Debrecen, Hungary.
authors.forename: Brigitta
authors.initials: B
authors.lastname: Oláh
authors.affiliation: Centre of Eye Research, Department of Ophthalmology, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Morten C
authors.initials: MC
authors.lastname: Moe
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Facskó
authors.affiliation: Stem Cells and Eye Research Laboratory, Department of Biochemistry and Molecular Biology, and MTA-DE Stem cell, Apoptosis and Genomics Research Group, University of Debrecen, Debrecen, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Fésüs
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, University of Szeged, Szeged, Hungary; Stem Cells and Eye Research Laboratory, Department of Biochemistry and Molecular Biology, and MTA-DE Stem cell, Apoptosis and Genomics Research Group, University of Debrecen, Debrecen, Hungary. Electronic address: petrovski.goran@med.u-szeged.hu.
authors.forename: Goran
authors.initials: G
authors.lastname: Petrovski
mesh_terms: D023102:Anoikis / Q000187:drug effects* / Q000235:genetics; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008268:Macular Degeneration / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D008297:Male; D010587:Phagocytosis / Q000187:drug effects* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000201:enzymology*; D014221:Triamcinolone / Q000494:pharmacology*; D000076202:c-Mer Tyrosine Kinase
chemical_list: D000893:Anti-Inflammatory Agents; D057134:Antibodies, Neutralizing; D005136:Eye Proteins; D011518:Proto-Oncogene Proteins; D014221:Triamcinolone; C097072:MERTK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase
keywords: AMD; Anoikis; Gas6; MERTK; Phagocytosis; Triamcinolone