First College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China; Department of Ophthalmology, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China.
First College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
J Photochem Photobiol B. 2018 Sep;186:9-16. doi: 10.1016/j.jphotobiol.2018.04.005. Epub 2018 Apr 6.
Long-term exposure to ultraviolet B (UVB) light increases the risk of UVB damage due to increased UVB absorption by the retina and may further lead to age-related eye diseases. The retinal pigment epithelium (RPE) cell is a main target of UVB reaching the retina; its degeneration is an essential event in UVB-mediated age-related macular degeneration (AMD). Herein, we first evaluated the expression and effect of iASPP, an inhibitory regulator of apoptosis, in UVB-induced RPE cell damage. Through the mechanism of RNA interference at the post-transcriptional level, miRNA affects a variety of cellular processes, including UVB-mediated cell damage. We next screened for upstream candidate miRNAs that may regulate iASPP expression. Among 8 candidate miRNAs, UVB significantly increased miR-340 levels. We also confirmed the direct binding of miR-340 to the 3'UTR of iASPP, and assessed the combined effect of miR-340 and iASPP on UVB-induced RPE cell damage. Taken together, we demonstrated the possible mechanisms involved in UVB-induced retinal damage. In RPE cells, UVB irradiation inhibits iASPP expression through inducing miR-340 expression, thereby promoting RPE cell apoptosis and suppressing cell viability via affecting p53, p21 and caspase-3 protein expression. Targeting miR-340 to rescue iASPP expression in RPE cells may help treat UVB-mediated retinal damage.
长期暴露于紫外线 B（UVB）会增加因视网膜对 UVB 吸收增加而导致的 UVB 损伤风险，并可能进一步导致与年龄相关的眼部疾病。视网膜色素上皮（RPE）细胞是到达视网膜的 UVB 的主要靶标；其退化是 UVB 介导的与年龄相关的黄斑变性（AMD）的一个重要事件。在此，我们首先评估了凋亡抑制因子（iASPP）的表达和作用，iASPP 是一种凋亡的抑制调节因子，在 UVB 诱导的 RPE 细胞损伤中。通过 RNA 干扰在转录后水平的机制，miRNA 影响多种细胞过程，包括 UVB 介导的细胞损伤。我们接下来筛选可能调节 iASPP 表达的上游候选 miRNA。在 8 个候选 miRNA 中，UVB 显著增加了 miR-340 的水平。我们还证实了 miR-340 与 iASPP 3'UTR 的直接结合，并评估了 miR-340 和 iASPP 的联合作用对 UVB 诱导的 RPE 细胞损伤的影响。总之，我们证明了可能涉及 UVB 诱导的视网膜损伤的机制。在 RPE 细胞中，UVB 照射通过诱导 miR-340 表达抑制 iASPP 表达，从而通过影响 p53、p21 和 caspase-3 蛋白表达促进 RPE 细胞凋亡并抑制细胞活力。针对 RPE 细胞中的 miR-340 以挽救 iASPP 表达可能有助于治疗 UVB 介导的视网膜损伤。
