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.

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).
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.
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.
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.
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.
AuthorsRéka Albert, Endre Kristóf, Gábor Zahuczky, Mária Szatmári-Tóth, Zoltán Veréb, Brigitta Oláh, Morten C Moe, Andrea Facskó, László Fésüs, Goran Petrovski
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1850 Issue 2 Pg. 435-46 (Feb 2015) ISSN: 0006-3002 [Print] Netherlands
PMID25450174 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014. Published by Elsevier B.V.
Chemical References
  • Anti-Inflammatory Agents
  • Antibodies, Neutralizing
  • Eye Proteins
  • Proto-Oncogene Proteins
  • Triamcinolone
  • MERTK protein, human
  • Receptor Protein-Tyrosine Kinases
  • Anoikis (drug effects, genetics)
  • Anti-Inflammatory Agents (pharmacology)
  • Antibodies, Neutralizing (pharmacology)
  • Cell Line
  • Epithelial Cells (cytology, enzymology)
  • Eye Proteins (biosynthesis, genetics)
  • Female
  • Gene Expression Regulation, Enzymologic (drug effects, genetics)
  • Gene Silencing (drug effects)
  • Humans
  • Macrophages (cytology, metabolism)
  • Macular Degeneration (drug therapy, enzymology, genetics)
  • Male
  • Phagocytosis (drug effects, genetics)
  • Proto-Oncogene Proteins (biosynthesis, genetics)
  • Receptor Protein-Tyrosine Kinases (biosynthesis, genetics)
  • Retinal Pigment Epithelium (cytology, enzymology)
  • Triamcinolone (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: