Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa.
Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa.
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DOI：
10.1186/gb-2007-8-11-r248
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发表时间：
2007
期刊：
影响因子：
12.3
通讯作者：
Farrar GJ
中科院分区：
文献类型：
--
作者：
Loscher CJ;Hokamp K;Kenna PF;Ivens AC;Humphries P;Palfi A;Farrar GJ
MicroRNA表达谱显示，携带视紫红质突变导致视网膜色素变性的小鼠的视网膜具有与野生型小鼠显着不同的microRNA谱；此外，在计算机分析中发现了差异调控microRNAs的潜在视网膜靶标。最近，microRNAs(MiRs)在发育和各种疾病状态等生理过程中所发挥的共同调节作用受到了重视。与Rho(编码视紫红质)相关的视网膜色素变性(RP)是最常见的遗传性视网膜变性，导致失明，目前还没有治疗方法。关于Rho内的突变与最终光感受器细胞通过凋亡而死亡的细胞机制，人们知之甚少。采用miR基因芯片技术和实时定量RT-PCR技术，对小鼠视网膜进行了miR基因表达谱分析。携带突变型Pro347Ser Rho基因的RP小鼠模型的视网膜和野生型视网膜、脑和全身的RNA样本(通过汇集八个不同小鼠器官的总RNA制备)显示出显著不同的miR图谱。视网膜特异的和最近描述的视网膜miRs在野生型小鼠视网膜中的表达是半定量的。与野生型视网膜相比，Pro347Ser中9个miRs的表达发生了2倍以上的变化(P<；0.05)。定量聚合酶链式反应证实，在Pro347Ser视网膜中，miR-1和miR-133的表达下降了2.5倍以上(P<；0.001)，而miR-96和miR-183的表达增加了3倍以上(P<；0.001)。这些MIR的潜在视网膜靶点是在Silico中预测的。这是第一个专注于评估视网膜疾病中miR表达变化的miR微阵列研究。此外，还鉴定了视网膜对miR-376a和miR-691的新偏好。这些结果有助于阐明MIR在正常和病变视网膜中的功能。调节视网膜miRs的表达可能代表未来视网膜病变(如RP)的治疗策略。
MicroRNA expression profiling showed that the retina of mice carrying a rhodopsin mutation that leads to retinitis pigmentosa have notably different microRNA profiles from wildtype mice; further in silico analyses identified potential retinal targets for differentially regulated microRNAs. The role played by microRNAs (miRs) as common regulators in physiologic processes such as development and various disease states was recently highlighted. Retinitis pigmentosa (RP) linked to RHO (which encodes rhodopsin) is the most frequent form of inherited retinal degeneration that leads to blindness, for which there are no current therapies. Little is known about the cellular mechanisms that connect mutations within RHO to eventual photoreceptor cell death by apoptosis. Global miR expression profiling using miR microarray technology and quantitative real-time RT-PCR (qPCR) was performed in mouse retinas. RNA samples from retina of a mouse model of RP carrying a mutant Pro347Ser RHO transgene and from wild-type retina, brain and a whole-body representation (prepared by pooling total RNA from eight different mouse organs) exhibited notably different miR profiles. Expression of retina-specific and recently described retinal miRs was semi-quantitatively demonstrated in wild-type mouse retina. Alterations greater than twofold were found in the expression of nine miRs in Pro347Ser as compared with wild-type retina (P < 0.05). Expression of miR-1 and miR-133 decreased by more than 2.5-fold (P < 0.001), whereas expression of miR-96 and miR-183 increased by more than 3-fold (P < 0.001) in Pro347Ser retinas, as validated by qPCR. Potential retinal targets for these miRs were predicted in silico. This is the first miR microarray study to focus on evaluating altered miR expression in retinal disease. Additionally, novel retinal preference for miR-376a and miR-691 was identified. The results obtained contribute toward elucidating the function of miRs in normal and diseased retina. Modulation of expression of retinal miRs may represent a future therapeutic strategy for retinopathies such as RP.
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影响因子：
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作者：
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