Visual arrestin modulates gene expression in the retinal pigment epithelium: Implications for homeostasis in the retina
Visual arrestin modulates gene expression in the retinal pigment epithelium: Implications for homeostasis in the retina
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视觉抑制蛋白调节视网膜色素上皮中的基因表达：对视网膜稳态的影响
DOI：
10.1016/j.bbrep.2019.100680
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发表时间：
2019
影响因子：
2.7
通讯作者：
Ohno-Matsui Kyoko
中科院分区：
文献类型：
--
作者：
Nagaoka Natsuko;Yoshida Takeshi;Cao Kejia;Iwasaki Yuko;Nakahama Ken-Ichi;Morita Ikuo;Ohno-Matsui Kyoko
视网膜色素上皮细胞（RPE）通过清除和回收膜中的光感受器外节（POS）来维持视网膜稳态。它还产生和分泌参与视网膜稳态的生长因子。Arrestin 1（ARR 1）是一种特异性表达于光感受器（PRs）的蛋白，是维持PRs和RPE之间视觉循环的重要分子。在本研究中，我们发现，ARR 1的表达减少形觉剥夺（FD）大鼠视网膜。在对照组RPE中检测到ARR 1，而在FD组RPE中未检测到ARR 1，这表明RPE吞噬细胞POS含有ARR 1。此外，我们在培养的人RPE中过表达ARR 1，并揭示ARR 1上调bFGF表达，下调TGF-β1，-β2和骨形态发生蛋白-2（BMP-2）。ARR 1上调bFGF直接影响PR的存活，而下调TGF-βs则抑制RPE的上皮间质转化（EMT），这是维持视网膜稳态的潜在机制。我们的研究结果还表明，调节RPE中ARR 1的表达可能成为各种眼部疾病的一种新的治疗选择。
The retinal pigment epithelium (RPE) is essential for maintaining retinal homeostasis by removing and recycling photoreceptor outer segment (POS) in membranes. It also produces and secretes growth factors involved in retinal homeostasis. Arrestin 1 (ARR1) is specifically expressed in photoreceptors (PRs) and a vital molecule for keeping visual cycle between PRs and RPE. In the present study, we showed the expression of ARR1 was decreased by form-deprivation (FD) in retina of rat. The ARR1 was detected in the RPE of the controls but not in the RPE of FD, which indicates RPE phagocytes POS containing ARR1. Furthermore, we overexpressed ARR1 in cultured human RPE and revealed the ARR1 upregulates bFGF expression and downregulates TGF-β1, -β2 and bone morphogenetic protein-2 (BMP-2). The upregulation of bFGF by ARR1 directly works for PR survival and the downregulation of TGF-βs by ARR1 inhibits epithelial mesenchymal transition (EMT) of RPE, which is the underlying mechanism of keeping retinal homeostasis. Our results also indicate the regulation of ARR1 expression in RPE might become a novel therapeutic option for various ocular diseases.