Biomarker driven drug repurposing for Fuchs’ Endothelial Corneal Dystrophy (FECD): A Computational study

Author:

Singh Sarangthem Dinamani1,Gogoi Gayatri1,Nagamani Selvaraman1,Bharali Pankaj1

Affiliation:

1. North East Institute of Science and Technology

Abstract

Abstract

Fuchs’ Endothelial Corneal Dystrophy (FECD) is a slowly advancing, non-inflammatory eye condition due to gradual increase in thickness of the Descemet’s membrane and the gradual decline in corneal endothelial cells population. It can occur sporadically or be inherited in an autosomal dominant manner leading to impaired vision over time. The only available method to treat FECD is corneal transplant. This study aims to identify potential biomarkers, pathways, and identifying therapeutic targets to treat FECD. The dataset GSE171830 was retrieved from Gene Expression Ominbus (GEO) database for the purpose of investigating and identifying potential therapeutic targets for FECD. Using GEO2R tool, 2654 differentially expressed genes (DEGs) were identified, with 1763 upregulated and 881 downregulated genes, for annotating FECD pathogenesis pathways. We conducted gene enrichment analysis with the aim of identifying the pathways associated with FECD disease. Further, a total of 61 FDA approved eye care drugs were docked with the identified biomarkers. Selected DEGs functional annotations show the involvement of several FECD related biological processes and pathways. Our findings unravel potential biomarkers including HLA-DRA, CSF1R, TNFRSF11B, COL4A1, etc. through GO, KEGG analysis, and Protein Protein Interaction (PPI). Molecular docking of 61 FDA-approved eye care drugs was performed and Naphazoline, Infigratinib, Lifitegrast, Netarsudil, Verteporfin, and Hyaluronic drugs were identified as repurposable candidates. The findings from this study could offer novel insights to the molecular mechanism of FECD and the identified drugs could play a significant impact on the treatment and prevention of FECD.

Publisher

Springer Science and Business Media LLC

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