Expression of VEGFA-regulating miRNAs and mortality in wet AMD
Expression of VEGFA-regulating miRNAs and mortality in wet AMD
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DOI：
10.1111/jcmm.14731
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发表时间：
2019-10-21
影响因子：
5.3
通讯作者：
Kaarniranta, Kai
中科院分区：
文献类型：
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作者：
Blasiak, Janusz;Watala, Cezary;Kaarniranta, Kai
microRNA（miRNAs）调节基因表达;其中许多作用于视网膜色素上皮（RPE），并且已知RPE变性是年龄相关性黄斑变性（AMD）的关键因素。反复注射抗VEGFA（血管内皮生长因子A）是湿性AMD的唯一有效疗法。我们研究了76名湿性AMD患者和70名对照者血清中参与VEGFA基因调控的18种miRNA表达之间的相关性。抗VEGFA治疗的有效性通过计算长达12年的注射次数进行评价。此外，我们还比较了AMD患者和对照组的相对死亡人数。我们观察到与对照组相比，湿性AMD患者中miR-34- 5 p、miR-126- 3 p、miR-145- 5 p和miR-205- 5 p的表达降低。这些miRNAs参与调节血管生成、细胞保护和蛋白质清除。没有miRNA与治疗结果显著相关。湿性AMD患者的死亡率高于对照组，并且他们的生存率与每年抗VEGFA注射次数呈负相关。未观察到miRNA表达与死亡率之间的相关性。我们的研究强调需要阐明miRNA调控在AMD发病机制中的作用。
MicroRNAs (miRNAs) regulate gene expression; many of them act in the retinal pigment epithelium (RPE), and RPE degeneration is known to be a critical factor in age-related macular degeneration (AMD). Repeated injections with anti-VEGFA (vascular endothelial growth factor A) are the only effective therapy in wet AMD. We investigated the correlation between the expression of 18 miRNAs involved in the regulation of the VEGFA gene in serum of 76 wet AMD patients and 70 controls. Efficacy of anti-VEGFA treatment was evaluated by counting the number of injections delivered up to 12 years. In addition, we compared the relative numbers of deaths in patient with AMD and control groups. We observed a decreased expression of miR-34-5p, miR-126-3p, miR-145-5p and miR-205-5p in wet AMD patients as compared with controls. These miRNAs are involved in the regulation of angiogenesis, cytoprotection and protein clearance. No miRNA was significantly correlated with the treatment outcome. Wet AMD patients had greater mortality than controls, and their survival was inversely associated with the number of anti-VEGFA injections per year. No association was observed between miRNA expression and mortality. Our study emphasizes the need to clarify the role of miRNA regulation in AMD pathogenesis.