Retinal Gene Expression Changes Related to IOP Exposure and Axonal Loss in DBA/2J Mice

Retinal Gene Expression Changes Related to IOP Exposure and Axonal Loss in DBA/2J Mice
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DOI:
10.1167/iovs.10-7063
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发表时间:
2011-10-01
影响因子:
4.4
通讯作者:
Danias, John
Danias, John
中科院分区:
医学2区
文献类型:
--
作者:
Panagis, Lambros;Zhao, Xiujun;Danias, John

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目的。确定累积眼压暴露和轴突损伤对 DBA/2 小鼠视网膜基因表达的影响。方法。使用 3 至 12 个月龄的 DBA/2J、DBA/2J(pe)(珍珠)和 C57BL/6 小鼠。使用回弹眼压计测量眼压,并通过视神经(ON)切片的分级来确定视神经(ON)损伤。对视网膜RNA进行微阵列分析。比较探讨了 DBA/2J 动物与 C57BL/6 和珍珠小鼠中累积 IOP 暴露 (cIOPx) 以及 ON 损伤 (ONd) 的影响。进行RT-PCR来确认一些基因并进行生物信息学分析来识别受影响的基因网络。结果。微阵列显示,在具有不同程度 ONd 的 9 个月和 12 个月 DBA/2J 小鼠中,越来越多的基因上调或下调。从 6 个月起,在相同年龄、具有不同 cIOPx 的眼睛之间,较少数量的基因出现差异表达。 DBA/2J动物与C57BL/6或珍珠小鼠之间分别有1385和1133个基因的表达存在差异,其中一些基因通过RT-PCR得到证实。生物信息学分析确定了功能基因网络,包括补体系统的成员,这些网络似乎与 cIOPx、ONd 或两者相关。结论。具有不同量的 cIOPx 和 ONd 的 DBA/2 小鼠的视网膜中发生基因表达变化。所涉及的基因编码具有多种细胞功能的蛋白质,其中包括补体系统。 cIOPx 和 ONd 影响常见和独特的基因集。 (投资眼科可见科学。2011;52:7807-7816)DOI:10.1167/iovs.10-7063
PURPOSE. To determine the effects of cumulative IOP exposure and axonal damage on retinal gene expression in DBA/2 mice.METHODS. DBA/2J, DBA/2J(pe) (pearl), and C57BL/6 mice from 3 to 12 months of age were used. IOP was measured with a rebound tonometer, and optic nerve (ON) damage was determined by grading of ON sections. Retinal RNA was subjected to microarray analysis. Comparisons explored the effects of cumulative IOP exposure (cIOPx) as well as ON damage (ONd) in the DBA/2J animals compared with that in the C57BL/6 and pearl mice. RT-PCR was performed to confirm some of the genes and bioinformatic analysis to identify affected gene networks.RESULTS. Microarrays revealed that an increasing number of genes were up-or downregulated in 9- and 12-month DBA/2J mice with various degrees of ONd. A smaller number of genes were expressed differentially between eyes with different cIOPx at the same age, from 6 months on. Expression of 1385 and 1133 genes differed between DBA/2J animals and C57BL/6 or pearl mice, respectively, and some them were confirmed by RT-PCR. Bioinformatics analysis identified functional gene networks, including members of the complement system, that appeared to be related to cIOPx, ONd, or both.CONCLUSIONS. Gene expression changes occur in retinas of DBA/2 mice with various amounts of cIOPx as well as ONd. Genes involved, code for proteins with diverse cellular functions and include among others the complement system. cIOPx and ONd affect common as well as unique gene sets. (Invest Ophthalmol Vis Sci. 2011;52:7807-7816) DOI:10.1167/iovs.10-7063