Gene Expression Signatures in Tree Shrew Sclera in Response to Three Myopiagenic Conditions
Gene Expression Signatures in Tree Shrew Sclera in Response to Three Myopiagenic Conditions
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DOI：
10.1167/iovs.13-12551
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发表时间：
2013-10-01
影响因子：
4.4
通讯作者：
Norton, Thomas T.
中科院分区：
文献类型：
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作者：
Guo, Lin;Frost, Michael R.;Norton, Thomas T.
目的.我们比较了三种不同视觉条件下树鼩巩膜中的基因表达特征，这些条件都能导致眼球延长和近视：负透镜佩戴，形觉剥夺和黑暗治疗。使用6组树鼩（每组n = 7）。从正常睁眼后24天（视觉体验天数[DVE]）开始，两个负透镜组配戴单眼-5屈光度（D）透镜2天（ML-2）或4天（ML-4）;两个形觉剥夺组配戴单眼半透明扩散镜2天（FD-2）或4天（FD-4）。暗处理组（DK）在经历光/暗环境后置于连续黑暗中11天，直到17 DVE。在28 DVE时检查正常集落饲养组。定量PCR用于测量巩膜中55个候选基因的mRNA水平的相对差异，这些候选基因要么是因为它们在先前的ML研究中显示出差异表达变化，要么是因为全转录组分析表明它们在近视发展过程中会发生变化。所有组中的治疗眼均出现显著的近视移位，表明近视正在积极进展。在ML-2组中，相对于对照眼，治疗眼中有27个基因显著下调。在FD-2组的治疗眼中，16个相同的基因也显著下调，一个上调。两种基因表达模式之间存在显著相关性（r（2）= 0.90，P < 0.001）。治疗4天后，ML-4组中31个基因显著下调，3个基因上调。在FD-4组中，29个相同的基因（26个下调和3个上调）和6个额外的基因（均下调）受到显著影响。反应模式高度相关（r（2）= 0.95，P < 0.001）。当DK组（右眼和左眼的平均值）与ML-4组的对照眼比较时，基因表达模式的方向和幅度与ML-4的那些相似（r（2）= 0.82，P < 0.001，不包括PENK）。当ML-4、FD-4和DK组的治疗眼与年龄匹配的正常眼进行比较时，也发现了类似的模式。在不同时间点由三种不同的近视源性视觉条件在巩膜中产生的非常相似的基因表达特征表明，在这种哺乳动物中存在与灵长类动物密切相关的“巩膜重塑特征”。巩膜基因检查没有区分特定的视觉刺激，启动信号级联反应，导致轴向伸长和近视。
PURPOSE. We compared gene expression signatures in tree shrew sclera produced by three different visual conditions that all produce ocular elongation and myopia: minus-lens wear, form deprivation, and dark treatment.METHODS. Six groups of tree shrews (n = 7 per group) were used. Starting 24 days after normal eye-opening (days of visual experience [DVE]), two minus-lens groups wore a monocular -5 diopter (D) lens for 2 days (ML-2) or 4 days (ML-4); two form-deprivation groups wore a monocular translucent diffuser for 2 days (FD-2) or 4 days (FD-4). A dark-treatment (DK) group was placed in continuous darkness for 11 days after experiencing a light/dark environment until 17 DVE. A normal colony-reared group was examined at 28 DVE. Quantitative PCR was used to measure the relative differences in mRNA levels for 55 candidate genes in the sclera that were selected, either because they showed differential expression changes in previous ML studies or because a whole-transcriptome analysis suggested they would change during myopia development.RESULTS. The treated eyes in all groups responded with a significant myopic shift, indicating that the myopia was actively progressing. In the ML-2 group, 27 genes were significantly downregulated in the treated eyes, relative to control eyes. In the treated eyes of the FD-2 group, 16 of the same genes also were significantly downregulated and one was upregulated. The two gene expression patterns were significantly correlated (r(2) = 0.90, P < 0.001). After 4 days of treatment, 31 genes were significantly downregulated in the treated eyes of the ML-4 group and three were upregulated. Twenty-nine of the same genes (26 down-and 3 upregulated) and six additional genes (all downregulated) were significantly affected in the FD-4 group. The response patterns were highly correlated (r(2) = 0.95, P < 0.001). When the DK group (mean of right and left eyes) was compared to the control eyes of the ML-4 group, the direction and magnitude of the gene expression patterns were similar to those of the ML-4 (r(2) = 0.82, P < 0.001, excluding PENK). Similar patterns also were found when the treated eyes of the ML-4, FD-4, and DK groups were compared to the age-matched normal eyes.CONCLUSIONS. The very similar gene expression signatures produced in the sclera by the three different myopiagenic visual conditions at different time points suggests that there is a "scleral remodeling signature" in this mammal, closely related to primates. The scleral genes examined did not distinguish between the specific visual stimuli that initiate the signaling cascade that results in axial elongation and myopia.