Estrogen genotoxicity causes preferential development of Fuchs endothelial corneal dystrophy in females.

ABSTRACT: Fuchs endothelial corneal dystrophy (FECD) is a genetically complex, age-related, female-predominant disorder characterized by loss of post-mitotic corneal endothelial cells (CEnCs). Ultraviolet-A (UVA) light has been shown to recapitulate the morphological and molecular changes seen in FECD to a greater extent in females than males, by triggering CYP1B1 upregulation in females. Herein, we investigated the mechanism of greater CEnC susceptibility to UVA in females by studying estrogen metabolism in response to UVA in the cornea. Loss of NAD(P)H quinone oxidoreductase 1 (NQO1) resulted in increased production of estrogen metabolites and mitochondrial-DNA adducts, with a higher CEnC loss in Nqo1^-/- female compared to wild-type male and female mice. The CYP1B1 inhibitors, trans-2,3

SUBMITTER: Kumar V 

PROVIDER: S-EPMC10716776 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature