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RNA 测序分析揭示了线粒体能量代谢改变和免疫细胞激活在形觉剥夺和晶状体诱导的小鼠近视中的作用。

RNA-Sequencing Analysis Reveals the Role of Mitochondrial Energy Metabolism Alterations and Immune Cell Activation in Form-Deprivation and Lens-Induced Myopia in Mice.

机构信息

Translational-Transdisciplinary Research Center, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul 05278, Republic of Korea.

Department of Medicine, Kyung Hee University College of Medicine, Seoul 02453, Republic of Korea.

出版信息

Genes (Basel). 2023 Nov 30;14(12):2163. doi: 10.3390/genes14122163.

DOI:10.3390/genes14122163
PMID:38136985
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10743199/
Abstract

Myopia is a substantial global public health concern primarily linked to the elongation of the axial length of the eyeball. While numerous animal models have been employed to investigate myopia, the specific contributions of genetic factors and the intricate signaling pathways involved remain incompletely understood. In this study, we conducted RNA-seq analysis to explore genes and pathways in two distinct myopia-inducing mouse models: form-deprivation myopia (FDM) and lens-induced myopia (LIM). Comparative analysis with a control group revealed significant differential expression of 2362 genes in FDM and 503 genes in LIM. Gene Set Enrichment Analysis (GSEA) identified a common immune-associated pathway between LIM and FDM, with LIM exhibiting more extensive interactions. Notably, downregulation was observed in OxPhos complex III of FDM and complex IV of LIM. Subunit A of complex I was downregulated in LIM but upregulated in FDM. Additionally, complex V was upregulated in LIM but downregulated in FDM. These findings suggest a connection between alterations in energy metabolism and immune cell activation, shedding light on a novel avenue for understanding myopia's pathophysiology. Our research underscores the necessity for a comprehensive approach to comprehending myopia development, which integrates insights from energy metabolism, oxidative stress, and immune response pathways.

摘要

近视是一个全球性的重大公共卫生问题,主要与眼球轴长的延长有关。虽然已经有许多动物模型被用于研究近视,但遗传因素的具体贡献和涉及的复杂信号通路仍不完全清楚。在这项研究中,我们进行了 RNA-seq 分析,以探索两种不同的诱导近视的小鼠模型(形觉剥夺性近视和离焦性近视)中的基因和通路。与对照组的比较分析显示,FDM 中有 2362 个基因和 LIM 中有 503 个基因存在显著差异表达。基因集富集分析(GSEA)发现 LIM 和 FDM 之间存在一个共同的免疫相关通路,而 LIM 表现出更广泛的相互作用。值得注意的是,FDM 中的 OxPhos 复合物 III 和 LIM 中的复合物 IV 出现下调。LIM 中的复合物 I 的亚基 A 下调,而 FDM 中则上调。此外,LIM 中的复合物 V 上调,而 FDM 中则下调。这些发现表明能量代谢和免疫细胞激活之间存在联系,为理解近视的病理生理学提供了新的途径。我们的研究强调了需要综合的方法来理解近视的发展,这需要整合能量代谢、氧化应激和免疫反应途径的见解。

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本文引用的文献

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Sci Transl Med. 2023 Aug 9;15(708):eabq1533. doi: 10.1126/scitranslmed.abq1533.
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Complement-mediated inflammation and mitochondrial energy metabolism in the proteomic profile of myopic human corneas.补体介导的炎症反应与近视人眼角膜蛋白质组谱中线粒体能量代谢
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The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest.
2023 年的 STRING 数据库:针对任何感兴趣的测序基因组的蛋白质-蛋白质关联网络和功能富集分析。
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