Progressive morphological changes and impaired retinal function associated with temporal regulation of gene expression after retinal ischemia/reperfusion injury in mice.
Progressive morphological changes and impaired retinal function associated with temporal regulation of gene expression after retinal ischemia/reperfusion injury in mice.
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DOI：
10.1186/1750-1326-8-21
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发表时间：
2013-06-22
影响因子：
15.1
通讯作者：
Clark AF
中科院分区：
文献类型：
--
作者：
Kim BJ;Braun TA;Wordinger RJ;Clark AF
视网膜缺血/再灌注（I/R）损伤是视力损害的重要原因。然而，问题仍然是对整体的I/R机制负责进行性损伤的视网膜。在这项研究中，我们使用了小鼠模型的I/R和特点的发病机制，通过分析视网膜的形态和功能的时间变化与视网膜基因表达的变化。通过将眼内压升高至120 mmHg持续60 min，然后通过恢复正常压力进行视网膜再灌注，在C57 BL/6小鼠的一只眼睛中诱导短暂缺血。在I/R后的不同时间点，通过用H & E染色的组织学评估和通过SD-OCT扫描来监测视网膜变化。视网膜功能也通过暗视ERG测量。使用cDNA微阵列和实时RT-PCR分析视网膜基因表达的时间变化。免疫组化观察视网膜神经节细胞和胶质增生。H & E染色和SD-OCT扫描显示，与对侧对照眼相比，I/R眼的视网膜厚度最初增加，随后显著减少，伴有细胞丢失。厚度减少最多的是内网状层（IPL）和内核层（INL）。在I/R损伤后第3天和第7天观察到视网膜脱离。与对侧对照眼相比，I/R眼的暗视ERG a-和b-波振幅和内隐时间显著受损。微阵列数据显示，涉及各种基因簇，如分子伴侣和炎症的基因表达的时间变化。此外，免疫组织化学染色证实了受损视网膜中的Müller细胞胶质增生。视网膜形态的时间依赖性变化与功能障碍和视网膜基因表达改变显著相关。我们证明了I/R介导的视网膜形态学变化与功能障碍以及视网膜基因表达的时间变化密切相关。我们的研究结果将提供进一步了解与视网膜缺血性损伤相关的分子发病机制。
Retinal ischemia/reperfusion (I/R) injury is an important cause of visual impairment. However, questions remain on the overall I/R mechanisms responsible for progressive damage to the retina. In this study, we used a mouse model of I/R and characterized the pathogenesis by analyzing temporal changes of retinal morphology and function associated with changes in retinal gene expression. Transient ischemia was induced in one eye of C57BL/6 mice by raising intraocular pressure to 120 mmHg for 60 min followed by retinal reperfusion by restoring normal pressure. At various time points post I/R, retinal changes were monitored by histological assessment with H&E staining and by SD-OCT scanning. Retinal function was also measured by scotopic ERG. Temporal changes in retinal gene expression were analyzed using cDNA microarrays and real-time RT-PCR. In addition, retinal ganglion cells and gliosis were observed by immunohistochemistry. H&E staining and SD-OCT scanning showed an initial increase followed by a significant reduction of retinal thickness in I/R eyes accompanied with cell loss compared to contralateral control eyes. The greatest reduction in thickness was in the inner plexiform layer (IPL) and inner nuclear layer (INL). Retinal detachment was observed at days 3 and 7 post- I/R injury. Scotopic ERG a- and b-wave amplitudes and implicit times were significantly impaired in I/R eyes compared to contralateral control eyes. Microarray data showed temporal changes in gene expression involving various gene clusters such as molecular chaperones and inflammation. Furthermore, immunohistochemical staining confirmed Müller cell gliosis in the damaged retinas. The time-dependent changes in retinal morphology were significantly associated with functional impairment and altered retinal gene expression. We demonstrated that I/R-mediated morphological changes the retina closely associated with functional impairment as well as temporal changes in retinal gene expression. Our findings will provide further understanding of molecular pathogenesis associated with ischemic injury to the retina.
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影响因子：
3.4
作者：
Cho, Jang-Hyeon;Mu, Xiuqian;Wang, Steven W.;Klein, William H.
通讯作者：
Klein, William H.
影响因子：
4.2
作者：
Chen, YG;Zhang, C;Tso, MOM
通讯作者：
Tso, MOM
影响因子：
4
作者：
Chiu, Kin;Zhou, Yuan;Chiu, Jin-Fu
通讯作者：
Chiu, Jin-Fu
影响因子：
5.3
作者：
Damiani, Devid;Alexander, John J.;Strettoi, Enrica
通讯作者：
Strettoi, Enrica
影响因子：
7.4
作者：
Dabkowski, Erinne R.;Williamson, Courtney L.;Hollander, John M.
通讯作者：
Hollander, John M.