Sex Differences in Congenital Hereditary Endothelial Dystrophy (CHED) and Slc4a11-/- Mouse Model of CHED

Here, we report the identification of sex differences in a cohort of 161 individuals with Corneal Hereditary Endothelial Dystrophy (CHED), a rare corneal endothelial dystrophy associated with biallelic SLC4A11 gene mutations, and in a Slc4a11-/- mouse model of CHED.

Male sex is associated with more severe corneal edema, the characteristic clinical feature of CHED, in affected individuals and Slc4a11-/- mice. The corneal endothelium in male Slc4a11-/- mice demonstrates increased levels of oxidative stress compared to female mice, evidenced by age-dependent higher levels of glucose- and glutamine-derived mitochondrial superoxide. Removal of gonadal hormones in Slc4a11-/- mice via gonadectomy increases corneal edema in female mice, suggesting a protective role for ovarian hormones.