Abstract
Purpose :
Serious transient and permanent visual loss occurs after sulfur mustard gas (SM) exposure to eyes. The mechanisms causing SM-induced blindness remain unknown. We sought to identify novel targets by analyzing differential gene expression (DGE), signaling pathways, and network analysis in naïve, SM-damaged, and SM-undamaged rabbit cornea RNA profiles.
Methods :
The mRNA sequences of naïve, SM-damaged, and SM-undamaged rabbit corneas 4-week post-SM exposure were generated using the Illumina-NextSeq deep sequencing tool (Omnibus accession # GSE127708). The RNA sequences of naïve (n=4), SM-damaged (n=5), and SM-undamaged (n=5) corneas underwent quality control profiling with FastQC. The DGE profiling was performed using widely distributed Python and R packages (Trimmomatic, HISAT2, StringTie, and DESeq2). The log2(FC)±2 and adjusted p value less than 0.05 were chosen to identify the most relevant genes.
Results :
The DGE analysis of the SM-damaged corneas compared with the naïve cornea yielded a total of 5930 differentially expressed genes (3196 up- and 2734 down-regulated). Compared to the naïve cornea group, the SM-undamaged corneas yielded 1884 differentially expressed genes (1029 up- and 855 down-regulated genes). When the SM-damaged corneas were compared with the SM-undamaged corneas, a total of 985 differentially expressed genes (308 up- and 677 down-regulated genes) were found. We identified 481 upregulated genes in cell proliferation and differentiation pathways in the SM-damaged fibrotic corneas. The DGE, pathway enrichment, and network analysis yielded fourteen potential target genes (CSF1R, ADIPOQ, CSF1, CCL11, ITGAM, ITGAX, HCK, IL1B, TNF, IL34, PTPRC, MMP9, MMP11) associated with SM-induced corneal damage.
Conclusions :
The identified fourteen novel most relevant genes have the potential to lead discovery of medical countermeasures to prevent/treat SM-induced corneal damage and vision loss.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.