Form-deprivation myopia in chick induces limited changes in retinal gene expression
Form-deprivation myopia in chick induces limited changes in retinal gene expression
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DOI：
10.1167/iovs.06-1538
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发表时间：
2007-08-01
影响因子：
4.4
通讯作者：
Stone, Richard A.
中科院分区：
文献类型：
--
作者：
McGlinn, Alice M.;Baldwin, Donald A.;Stone, Richard A.
目的。有证据表明，视网膜是屈光发育的主要控制者。在本研究中，通过分析视网膜转录组，以确定与形觉剥夺性近视相关的基因表达和潜在的信号通路的变化。方法：1周龄的白色来航鸡戴着单侧图像退化护目镜6小时或3天(n=6)。来自视网膜/(视网膜色素上皮)的总RNA用于鸡基因芯片(鸡基因芯片；Affymetrix，Santa Clara，CA)的表达谱分析。为了确定戴护目镜和不戴护目镜的眼的基因表达水平的差异，采用微阵列显著性分析(SAM)方法对归一化微阵列信号强度进行分析。通过实时定量逆转录聚合酶链式反应(QPCR)验证独立生物复制体的差异表达基因。结果：形体剥夺眼的差异表达基因检测到微小变化。在佩戴护目镜6小时的鸡中，证实了骨形态发生蛋白2和结缔组织生长因子的下调。在佩戴护目镜3天的患者中，骨形态发生蛋白2、血管活性肠肽、前降压素II相关肽和丝裂原激活蛋白激酶磷酸酶2下调，B型内皮素受体和白细胞介素18上调。结论：形觉剥夺性近视在其早期阶段，只有在转录组水平上视网膜基因表达的微小变化。虽然验证基因的名单很短，但每个基因都值得进一步研究，因为它们可能参与了调节近视发展的信号级联。
PURPOSE. Evidence has implicated the retina as a principal controller of refractive development. In the present study, the retinal transcriptome was analyzed to identify alterations in gene expression and potential signaling pathways involved in form-deprivation myopia of the chick.METHODS. One-week-old white Leghorn chicks wore a unilateral image- degrading goggle for 6 hours or 3 days (n = 6 at each time). Total RNA from the retina/(retinal pigment epithelium) was used for expression profiling with chicken gene microarrays (Chicken GeneChips; Affymetrix, Santa Clara, CA). To identify gene expression level differences between goggled and contralateral nongoggled eyes, normalized microarray signal intensities were analyzed by the significance analysis of microarrays (SAM) approach. Differentially expressed genes were validated by real-time quantitative reverse transcription polymerase chain reaction (qPCR) in independent biological replicates.RESULTS. Small changes were detected in differentially expressed genes in form-deprived eyes. In chickens that had 6 hours of goggle wear, downregulation of bone morphogenetic protein 2 and connective tissue growth factor was validated. In those with 3 days of goggle wear, downregulation of bone morphogenetic protein 2, vasoactive intestinal peptide, preopro-urotensin II-related peptide and mitogen-activated protein kinase phosphatase 2 was validated, and upregulation of endothelin receptor type B and interleukin-18 was validated.CONCLUSIONS. Form- deprivation myopia, in its early stages, is associated with only minimal changes in retinal gene expression at the level of the transcriptome. While the list of validated genes is short, each merits further study for potential involvement in the signaling cascade mediating myopia development.