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

ABSTRACT: Sex differences have been described in several corneal diseases such as Fuchs endothelial corneal dystrophy and keratoconus, with estrogens implicated in the induction of these differences. 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. Transcriptomic analysis of corneal endothelium and body composition analysis in Slc4a11+/+ and Slc4a11-/- mice suggest that estrogens play a role in promoting corneal endothelial utilization of lipids via β-oxidation as an alternative energy source in the setting of decreased SLC4A11, thereby reducing oxidative stress from glucose and glutamine metabolism.

ORGANISM(S): Mus musculus

PROVIDER: GSE288029 | GEO | 2026/05/15

REPOSITORIES: GEO

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