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佩戴隐形眼镜会改变角膜上皮和细菌对(此处原文缺失具体内容)的转录反应。

Contact Lens Wear Alters Transcriptional Responses to in Both the Corneal Epithelium and the Bacteria.

作者信息

Kumar Naren G, Grosser Melinda R, Wan Stephanie, Schator Daniel, Ahn Eugene, Jedel Eric, Nieto Vincent, Evans David J, Fleiszig Suzanne M J

机构信息

Herbert Wertheim School of Optometry & Vision Science, University of California, Berkeley, CA USA.

Graduate Program in Infectious Diseases and Immunity, University of California, Berkeley, CA USA.

出版信息

bioRxiv. 2024 Dec 4:2024.12.03.626720. doi: 10.1101/2024.12.03.626720.

Abstract

PURPOSE

Healthy corneas resist colonization by virtually all microbes yet contact lens wear can predispose the cornea to sight-threatening infection with . Here, we explored how lens wear changes corneal epithelium transcriptional responses to and its impact on bacterial gene expression.

METHODS

Male and female C57BL/6J mice were fitted with a contact lens on one eye for 24 h. After lens removal, corneas were immediately challenged for 4 h with . A separate group of naïve mice were similarly challenged with bacteria. Bacteria-challenged eyes were compared to uninoculated naive controls as was lens wear alone. Total RNA-sequencing determined corneal epithelium and bacterial gene expression.

RESULTS

Prior lens wear profoundly altered the corneal response to , including: upregulated pattern-recognition receptors (), downregulated lectin pathway of complement activation (), amplified upregulation of , (immune defense) and further suppression of (corneal stromal integrity). Without lens wear, upregulated mitochondrial and ubiquinone metabolism genes. Lens wear alone upregulated (immune defense) and downregulated Ca2-dependent genes . exposure to prior lens wearing vs. naïve corneas upregulated bacterial genes of virulence (), its regulation (, PA1226) and antimicrobial resistance (, ).

CONCLUSION

Prior lens wear impacts corneal epithelium gene expression altering its responses to and how responds to it favoring virulence, survival and adaptation. Impacted genes and associated networks provide avenues for research to better understand infection pathogenesis.

摘要

目的

健康的角膜实际上能抵抗所有微生物的定植,但佩戴隐形眼镜会使角膜易受威胁视力的感染。在此,我们探讨了佩戴隐形眼镜如何改变角膜上皮对[细菌名称未给出]的转录反应及其对细菌基因表达的影响。

方法

将雄性和雌性C57BL/6J小鼠的一只眼睛佩戴隐形眼镜24小时。取下隐形眼镜后,立即用[细菌名称未给出]对角膜进行4小时的攻击。另一组未接触过的小鼠同样用细菌进行攻击。将受到细菌攻击的眼睛与未接种的未接触过的对照进行比较,佩戴隐形眼镜的情况也进行了比较。全RNA测序确定角膜上皮和细菌基因表达。

结果

先前佩戴隐形眼镜深刻改变了角膜对[细菌名称未给出]的反应,包括:上调模式识别受体([具体受体名称未给出]),下调补体激活的凝集素途径([具体途径名称未给出]),放大[具体基因名称未给出]、[具体基因名称未给出](免疫防御)的上调以及进一步抑制[具体基因名称未给出](角膜基质完整性)。在未佩戴隐形眼镜的情况下,[细菌名称未给出]上调线粒体和泛醌代谢基因。仅佩戴隐形眼镜上调[具体基因名称未给出](免疫防御)并下调钙依赖性基因[具体基因名称未给出]。与未接触过的角膜相比,先前佩戴隐形眼镜后接触[细菌名称未给出]上调了细菌的毒力基因([具体基因名称未给出])、其调控基因([具体基因名称未给出]、PA1226)和抗微生物抗性基因([具体基因名称未给出]、[具体基因名称未给出])。

结论

先前佩戴隐形眼镜会影响角膜上皮基因表达,改变其对[细菌名称未给出]的反应以及[细菌名称未给出]对其的反应,有利于毒力、存活和适应。受影响的基因和相关网络为更好地理解感染发病机制的研究提供了途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a80a/11643048/fc0c435a5996/nihpp-2024.12.03.626720v1-f0001.jpg

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