TUDCA Promotes Phagocytosis by Retinal Pigment Epithelium via MerTK Activation
TUDCA Promotes Phagocytosis by Retinal Pigment Epithelium via MerTK Activation
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DOI：
10.1167/iovs.14-15962
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发表时间：
2015-04-01
影响因子：
4.4
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
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作者：
Murase, Hiromi;Tsuruma, Kazuhiro;Hara, Hideaki
目的.视网膜色素上皮细胞对老化感光细胞外节（POS）的更新和清除是一个日常节律性过程，对长期视力很重要。吞噬功能障碍导致感光细胞死亡。牛磺熊去氧胆酸（TUDCA）是一种内源性胆汁酸，已知在中风、神经系统疾病和视网膜变性模型中显示出神经保护作用。在这项研究中，我们研究了TUDCA对视网膜吞噬功能的影响。我们使用pH敏感的荧光染料pHrodo-琥珀酰亚胺酯（SE）来标记POS以监测吞噬作用。摄入后，由于脂质体内部的pH变化，pHrodo荧光的强度增加。RPE细胞系，ARPE-19，和原代人RPE细胞被用来研究过氧化氢（H2 O2）诱导的破坏吞噬作用的pH敏感性荧光POS吞噬试验。此外，我们还研究了TUDCA是否能促进吞噬功能。pHrodo光发射强度随时间增加而增加。牛磺熊去氧胆酸增强POS的吞噬功能，并对H（2）O（2-）诱导的吞噬功能障碍有保护作用。它还通过激活Mer酪氨酸激酶受体（MerTK）促进吞噬功能，已知MerTK在POS的生理更新中具有关键作用。这些结果表明，TUDCA激活MerTK，这对POS的吞噬作用很重要。牛磺熊去氧胆酸可能是治疗视网膜疾病的一种新的治疗选择。
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.