Transcriptome Analysis of Long-Term Exposure to Blue Light in Retinal Pigment Epithelial Cells.
Transcriptome Analysis of Long-Term Exposure to Blue Light in Retinal Pigment Epithelial Cells.
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DOI：
10.4062/biomolther.2021.155
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发表时间：
2022-05-01
影响因子：
3.7
通讯作者：
Jeong KW
中科院分区：
文献类型：
--
作者：
Jin HL;Jeong KW
干性年龄相关性黄斑变性（AMD）是一种进行性失明，主要是由于视网膜色素上皮（RPE）功能障碍和丧失。视觉周期的副产物N-亚视黄基-N-视黄基乙醇胺（A2 E）的积累引起损害视力的RPE和感光细胞变性。已经使用视网膜色素上皮中A2 E积累的蓝光模型和来自AMD患者的视网膜组织的转录组学研究鉴定了与干性AMD相关的基因。然而，干性黄斑变性进展缓慢，目前的方法不能根据AMD进展的阶段揭示基因转录的变化。因此，它们在鉴定致病基因方面受到限制。在这里，我们创建了一个长期暴露的模型，以确定暴露于蓝光和非细胞毒性剂量的A2 E 120天的人视网膜色素上皮细胞（ARPE-19）中诱导的基因表达的时间依赖性变化。我们分别在40、100和120天鉴定了阶段特异性基因。A2 E和蓝光显著改变了早期上皮-间质转化（EMT）相关基因、中期糖酵解和血管生成相关基因以及晚期凋亡和炎症相关基因的表达。EMT晚期基因表达的变化与晚期AMD人眼中发现的相似。我们的研究结果为进一步了解蓝光诱导的干性AMD的发病机制提供了新的体外模型，未来可以通过该模型鉴定相关基因。
Dry age-related macular degeneration (AMD) is a type of progressive blindness that is primarily due to dysfunction and the loss of retinal pigment epithelium (RPE). The accumulation of N-retinylidene-N-retinylethanolamine (A2E), a by-product of the visual cycle, causes RPE and photoreceptor degeneration that impairs vision. Genes associated with dry AMD have been identified using a blue light model of A2E accumulation in the retinal pigment epithelium and transcriptomic studies of retinal tissue from patients with AMD. However, dry macular degeneration progresses slowly, and current approaches cannot reveal changes in gene transcription according to stages of AMD progression. Thus, they are limited in terms of identifying genes responsible for pathogenesis. Here, we created a model of long-term exposure to identify temporally-dependent changes in gene expression induced in human retinal pigment epithelial cells (ARPE-19) exposed to blue light and a non-cytotoxic dose of A2E for 120 days. We identified stage-specific genes at 40, 100, and 120 days, respectively. The expression of genes corresponding to epithelial-mesenchymal transition (EMT) during the early stage, glycolysis and angiogenesis during the middle stage, and apoptosis and inflammation pathways during the late stage was significantly altered by A2E and blue light. Changes in the expression of genes at the late stages of the EMT were similar to those found in human eyes with late-stage AMD. Our results provide further insight into the pathogenesis of dry AMD induced by blue light and a novel model in vitro with which relevant genes can be identified in the future.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
4.5
作者：
Lee, Bom-Lee;Kang, Jung-Hwan;Choung, Se-Young
通讯作者：
Choung, Se-Young
影响因子：
5.6
作者：
Lin, Cheng-Hui;Wu, Man-Ru;Cheng, Yu-Wen
通讯作者：
Cheng, Yu-Wen
影响因子：
6.1
作者：
Alaimo, Agustina;Garcia Linares, Guadalupe;Lidia Kotler, Monica
通讯作者：
Lidia Kotler, Monica
影响因子：
13.7
作者：
Holz, Frank G.;Strauss, Erich C.;Campagne, Menno van Lookeren
通讯作者：
Campagne, Menno van Lookeren