Integrative transcriptomics analysis and experimental validation reveal immunomodulatory patterns in keratoconus

作者：Xi Chen, Chang Liu, Zedu Cui, Yuke Huang, Qian Luo, Shuilian Chen, Xiao Wang, Xiangtao Hou, Qian Gong, Yan Li, Jin Qiu, Yuxin Zhang, Pei Chen, Ying Yang, Jing Zhuang, Keming Yu · 发表于：Experimental Eye Research · 年份：2023 · DOI：10.1016/j.exer.2023.109460 · 被引用次数：14 · 研究领域：Corneal surgery and disorders、Corneal Surgery and Treatments、Ocular Surface and Contact Lens

Keratoconus is a progressive disorder of the cornea and is typically considered a noninflammatory disease. However, increasing evidence indicates that immune disorders play an essential role in keratoconus progression, but the immune-related etiology remains elusive. Here, we comprehensively utilized bioinformatics approaches and experimental methods to explore the potential immunoregulatory mechanism of keratoconus progression. Transcriptomics data containing two keratoconus patient groups was derived from the public dataset GSE151631. The intersection of genes and known immunological genes was used to obtain differentially expressed immune-related genes. We utilized various protein clustering algorithms to screen out and validated the hub immune-related genes, and further explored their potential biological functions via gene annotation and pathway enrichment analyses. Moreover, the underlying immune landscape and drug targets were predicted by immune cell infiltration analysis and drug-gene interaction analysis. Furthermore, keratoconus-related immunoregulatory competitive endogenous RNA networks were constructed and experimentally validated. After filtering and experimental validation, nine keratoconus-associated immune-related genes were credible. Infiltrated monocytes might play an essential role in the progression of keratoconus. Moreover, eleven intersecting drugs targeting four genes, CCR2, CCR5, F2RL1, and ADORA1, were considered as potential druggable molecular tar...