Genome-Wide Scleral Micro- and Messenger-RNA Regulation During Myopia Development in the Mouse.
Genome-Wide Scleral Micro- and Messenger-RNA Regulation During Myopia Development in the Mouse.
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DOI：
10.1167/iovs.16-19563
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发表时间：
2016-11-01
影响因子：
4.4
通讯作者：
Wildsoet CF
中科院分区：
文献类型：
--
作者：
Metlapally R;Park HN;Chakraborty R;Wang KK;Tan CC;Light JG;Pardue MT;Wildsoet CF
MicroRNA (miRNA) 先前已被证实与正常眼睛生长中的巩膜重塑有关。它们有可能成为通过调节巩膜基质重塑来预防/延缓近视眼过度生长的治疗靶点。为了探索这种潜力，研究了小鼠近视眼和对照眼的全基因组 miRNA 和信使 RNA (mRNA) 巩膜谱。在 12L:12D 周期下饲养的 C57BL/6J 小鼠 (n = 7; P28) 单侧形觉剥夺 (FD) 2 周。分别使用光折射和 1310 nm 谱域光学相干断层扫描测量屈光不正和眼轴长度变化。对来自 FD 和对照眼的巩膜 RNA 样本进行处理以进行微阵列分析。使用国家老化研究所阵列分析工具进行统计分析；使用方差分析进行组间比较，并使用网络上提供的软件识别基因本体。研究结果在另一组小鼠 (n = 7) 中使用定量 PCR 得到证实。形觉剥夺眼的屈光不正显示近视变化（−2.02 ± 0.47 D；P < 0.01）。测试眼与对照眼巩膜 RNA 谱的比较显示，54 个差异表达的 miRNA 和 261 个 mRNA 倍数变化 >1.25（miRNA 和 mRNA 的最大倍数变化分别 = 1.63 和 2.7）（P < 0.05；最小值，P = 0.0001）。显示基因过度表达的重要本体论（P < 0.05）包括中间丝组织、支架蛋白结合、刺激检测、钙离子、G 蛋白和光转导。证实了 Let-7a 和 miR-16-2 以及 Smok4a、Prph2 和 Gnat1 的显着差异表达。巩膜 mi- 和 mRNA 显示出与近视相关的差异表达，支持 miRNA 参与眼睛生长调节。观察到的相对较小倍数变化的总体趋势表明巩膜基因表达存在严格控制的调节机制。
MicroRNA (miRNAs) have been previously implicated in scleral remodeling in normal eye growth. They have the potential to be therapeutic targets for prevention/retardation of exaggerated eye growth in myopia by modulating scleral matrix remodeling. To explore this potential, genome-wide miRNA and messenger RNA (mRNA) scleral profiles in myopic and control eyes from mice were studied. C57BL/6J mice (n = 7; P28) reared under a 12L:12D cycle were form-deprived (FD) unilaterally for 2 weeks. Refractive error and axial length changes were measured using photorefraction and 1310-nm spectral-domain optical coherence tomography, respectively. Scleral RNA samples from FD and fellow control eyes were processed for microarray assay. Statistical analyses were performed using National Institute of Aging array analysis tool; group comparisons were made using ANOVA, and gene ontologies were identified using software available on the Web. Findings were confirmed using quantitative PCR in a separate group of mice (n = 7). Form-deprived eyes showed myopic shifts in refractive error (−2.02 ± 0.47 D; P < 0.01). Comparison of the scleral RNA profiles of test eyes with those of control eyes revealed 54 differentially expressed miRNAs and 261 mRNAs fold-change >1.25 (maximum fold change = 1.63 and 2.7 for miRNAs and mRNAs, respectively) (P < 0.05; minimum, P = 0.0001). Significant ontologies showing gene over-representation (P < 0.05) included intermediate filament organization, scaffold protein binding, detection of stimuli, calcium ion, G protein, and phototransduction. Significant differential expression of Let-7a and miR-16-2, and Smok4a, Prph2, and Gnat1 were confirmed. Scleral mi- and mRNAs showed differential expression linked to myopia, supporting the involvement of miRNAs in eye growth regulation. The observed general trend of relatively small fold-changes suggests a tightly controlled, regulatory mechanism for scleral gene expression.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
3
作者：
Gaidatzis D;van Nimwegen E;Hausser J;Zavolan M
通讯作者：
Zavolan M
影响因子：
4.4
作者：
Guo, Lin;Frost, Michael R.;Norton, Thomas T.
通讯作者：
Norton, Thomas T.
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
影响因子：
3.4
作者：
Gentle, A;McBrien, NA
通讯作者：
McBrien, NA