title: TUDCA Promotes Phagocytosis by Retinal Pigment Epithelium via MerTK Activation.
abstract: OBJECTIVE
  Renewal and elimination of the aged photoreceptor outer segment (POS) by RPE cells is a daily rhythmic process that is important for long-term vision. Phagocytic dysfunction results in photoreceptor cell death. Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, is known to show neuroprotective effects in stroke, neurological diseases, and retinal degeneration models. In this study, we investigated the effects of TUDCA on retinal phagocytosis.
  
  
  METHODS
  We used pHrodo-succinimidyl ester (SE), a pH-sensitive fluorescent dye, to label the POS for monitoring phagocytosis. After ingestion, the intensity of pHrodo fluorescence increases because of the pH changes inside the liposome. An RPE cell line, ARPE-19, and primary human RPE cells were used to investigate the hydrogen peroxide (H2O2)-induced disruption of phagocytosis in the pH-sensitive fluorescence POS phagocytosis assay. Additionally, we examined whether TUDCA could promote phagocytic function.
  
  
  RESULTS
  The intensity of pHrodo light emission increased in a time-dependent manner. Tauroursodeoxycholic acid enhanced phagocytosis of POS and protected against H2O2-induced phagocytic dysfunction. It also promoted phagocytic function via activation of Mer tyrosine kinase receptor (MerTK), which is known to have a key role in the physiological renewal of POS.
  
  
  CONCLUSIONS
  These results suggest that TUDCA activates MerTK, which is important for phagocytosis of POS. Tauroursodeoxycholic acid may represent a new therapeutic option for the treatment of retinal diseases.
authors: Hiromi
authors: H
authors: Murase
authors: Kazuhiro
authors: K
authors: Tsuruma
authors: Masamitsu
authors: M
authors: Shimazawa
authors: Hideaki
authors: H
authors: Hara
mesh_terms: D000368:Aged; D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D002478:Cells, Cultured; D006801:Humans; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000187:drug effects / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013552:Swine; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D000076202:c-Mer Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; C097072:MERTK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase