Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 56, Issue 4, Pages 2511-2518Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.14-15962
Keywords
phagocytosis; TUDCA; retinal pigment epithelium
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Funding
- Gifu Pharmaceutical University
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PURPOSE. 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 H(2)O(2-)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.
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