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Xi Chen, Chang Liu, Jing Zhuang, Keming Yu; Consistent Immunomodulatory Genes and the Competitive Endogenous RNA Networks in Keratoconus among Populations. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2411 – A0214.
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© ARVO (1962-2015); The Authors (2016-present)
Keratoconus (KC) is a progressive disorder of the cornea. Increasing evidence indicates that immune disorders play an essential role in KC progression. In addition, the manifestations of KC vary across populations. However, the immune-related etiology and concordant regulatory mechanisms in different populations remain elusive. Here, we comprehensively utilized bioinformatics approaches and experimental methods to explore the potential immunoregulatory mechanism of KC progression among populations.
Transcriptomics data contains two KC populations was derived from the public dataset GSE151631 (America: N=11; Saudi Arabia: N=15). Taking the intersection of genes across populations and known immunological genes to obtain immune-related differentially expressed genes (IRGs). Protein clustering algorithms were utilized to screen out the hub IRGs, which were further verified in the third populations (China: N=8). The underlying drug targets were predicted by drug-gene interaction analysis. Additionally, the KC-related immunoregulatory competitive endogenous RNAs networks (ceRNA) were constructed and experimentally validated.
Overall, KC-associated common differentially expressed IRGs were obtained. After experimental validation, 15 hub IRGs were credible and not related to populations. Moreover, a total of 9 intersecting drugs targeting three genes, CCR2, CCR5, and F2RL1, were considered as potential druggable molecular targets for KC. Furthermore, upon ceRNA interaction network, we identified several lncRNAs and miRNAs as critical non-coding RNAs regulating the shared IRGs in different populations of KC patients.
The current study facilitated the understanding of KC-related immune processes and provided novel insights into developing new immunotherapies for KC. Moreover, finding commonalities in the onset and progression of KC in different populations would facilitate the generalizability of treatment.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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