Abstract
Purpose :
The prevalence of Fuchs endothelial corneal dystrophy (FECD) is higher in females than in males, but the underlying mechanisms remain unelucidated. We hypothesized that this difference in prevalence is related to the variations of sex-biased gene expression in corneal endothelial cells (CECs). This present study aims to examine the sex-biased gene expressions in CECs by RNA sequencing (RNA-Seq) analysis.
Methods :
Our previously reported RNA-Seq data of human CECs from 7 normal healthy subjects (3 males and 4 females) (Tokuda Y, et al. Sci Data, 2020) were utilized. Differentially expressed genes (DEGs) were identified with the thresholds of P-value (< 0.01) and |Log2 Fold Change| (> 1.0) cut-offs. The difference of gene expression patterns between female and male groups was investigated via heatmap plotting and principal component analysis (PCA). Gene Ontology (GO) analysis was also conducted to investigate the functions of sex-biased genes.
Results :
Among a total of 60,164 subjected genes, 338 DEGs including 142 upregulated and 196 downregulated genes were identified in the female group compared to the male group. Heatmap plotting and PCA revealed that gene expression patterns differed distinctly between sexes. GO analysis indicated that the altered genes between the female and male groups were associated with response to a steroid hormone, myelination, leukocyte migration, and regulation of interleukin (IL)-6 and IL-8 production. In addition, 13 DEGs on the X chromosome were identified, and all 13 DEGs were higher in the female than in the male group.
Conclusions :
We first demonstrated that the gene expression pattern in CECs differs between healthy female and male subjects. Although it is hypothetical, sex-biased genes in CECs is potentially involved in the high prevalence of FECD in female.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.