Analysis of Glaucoma Associated Genes in Response to Inflammation, an Examination of a Public Data Set Derived from Peripheral Blood from Patients with Hepatitis C.
Analysis of Glaucoma Associated Genes in Response to Inflammation, an Examination of a Public Data Set Derived from Peripheral Blood from Patients with Hepatitis C.
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DOI：
10.2147/opth.s364739
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发表时间：
2022
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青光眼是全球第二大失明原因，尽管其发病率很高，但与其发病机制有关的许多问题仍有待解答。有证据表明氧化应激和炎症在疾病进展中发挥着重要作用。多项研究显示青光眼患者的白细胞基因表达发生改变，揭示了使用外周生物标志物来诊断或分期青光眼的可能性。青光眼与远离视网膜的组织中的基因表达变化相关这一事实强调了全身氧化应激和炎症可能参与青光眼的潜在促成或复合因素。我们根据文献综述整理了一份与青光眼相关的氧化应激和炎症标志物列表。此外，我们还利用了从两个患者组的外周血单核细胞和巨噬细胞中收集的基因表达值的公开数据集：丙型肝炎病毒慢性感染者和已清除丙型肝炎病毒的患者。先天免疫反应的激活可以使细胞或组织对第二次延迟的促炎刺激更加敏感。在随后的聚肌苷：聚胞苷酸处理后，这些细胞的额外基因表达数据用于引发急性炎症反应，从而可以研究这些组中的急性炎症反应。我们使用两个患者组之间的倍数变化比较值来识别感兴趣的基因。比较分析确定了 17 种青光眼生物标志物，它们在 HCV 介导的炎症反应中存在差异表达。在这 17 例中，有 6 例的基线值与治疗值相比具有显着的 p 值。对已清除丙型肝炎病毒的患者与未清除丙型肝炎病毒的患者之间的这些基因的表达数据进行了比较，并确定了三个值得进一步研究的基因。这些结果支持我们的假设，即丙型肝炎病毒感染继发的炎症影响与抗氧化反应和炎症相关的青光眼生物标志物基因的表达。此外，它们还为进一步研究了解病毒感染的先天反应与青光眼炎症方面之间的关系提供了几个潜在的目标，并有可能用作青光眼的预测生物标志物或药物干预。
Glaucoma is the second leading cause of blindness worldwide and despite its prevalence, there are still many unanswered questions related to its pathogenesis. There is evidence that oxidative stress and inflammation play a major role in disease progression. Glaucoma patients from several studies showed altered gene expression in leukocytes, revealing the possibility of using peripheral biomarkers to diagnose or stage glaucoma. The fact that glaucoma is associated with gene expression changes in tissues distant from the retina underscores the possible involvement of systemic oxidative stress and inflammation as potential contributing or compounding factors in glaucoma. We assembled a list of oxidative stress and inflammatory markers related to glaucoma based on a review of the literature. In addition, we utilized publicly available data sets of gene expression values collected from peripheral blood mononuclear cells and macrophages from two patient groups: those chronically infected by the hepatitis C virus and those who have cleared it. Activation of the innate immune response can render cells or tissues more responsive to a second delayed proinflammatory stimulus. Additional gene expression data from these cells after subsequent polyinosinic:polycytidylic acid treatment, used to elicit an acute inflammatory response, allowed for the investigation of the acute inflammatory response in these groups. We used fold-change comparison values between the two patient groups to identify genes of interest. A comparison analysis identified 17 glaucoma biomarkers that were differentially expressed in response to HCV-mediated inflammation. Of these 17, six had significant p-values in the baseline vs treated values. Expression data of these genes were compared between patients who had cleared the Hepatitis C virus versus those who had not and identified three genes of interest for further study. These results support our hypothesis that inflammation secondary to Hepatitis C virus infection affects the expression of glaucoma biomarker genes related to the antioxidant response and inflammation. In addition, they provide several potential targets for further research into understanding the relationship between innate responses to viral infection and inflammatory aspects of glaucoma and for potential use as a predictive biomarker or pharmacological intervention in glaucoma.