@article {1478328,
	title = {Ultraviolet A light induces DNA damage and estrogen-DNA adducts in Fuchs endothelial corneal dystrophy causing females to be more affected},
	journal = {Proc Natl Acad Sci U S A},
	volume = {117},
	number = {1},
	year = {2020},
	month = {2020 Jan 07},
	pages = {573-583},
	abstract = {Fuchs endothelial corneal dystrophy (FECD) is a leading cause of corneal endothelial (CE) degeneration resulting in impaired visual acuity. It is a genetically complex and age-related disorder, with higher incidence in females. In this study, we established a nongenetic FECD animal model based on the physiologic outcome of CE susceptibility to oxidative stress by demonstrating that corneal exposure to ultraviolet A (UVA) recapitulates the morphological and molecular changes of FECD. Targeted irradiation of mouse corneas with UVA induced reactive oxygen species (ROS) production in the aqueous humor, and caused greater CE cell loss, including loss of ZO-1 junctional contacts and corneal edema, in female than male mice, characteristic of late-onset FECD. UVA irradiation caused greater mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage in female mice, indicative of the sex-driven differential response of the CE to UVA, thus accounting for more severe phenotype in females. The sex-dependent effect of UVA was driven by the activation of estrogen-metabolizing enzyme CYP1B1 and formation of reactive estrogen metabolites and estrogen-DNA adducts in female but not male mice. Supplementation of -acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS), diminished the morphological and molecular changes induced by UVA in vivo. This study investigates the molecular mechanisms of environmental factors in FECD pathogenesis and demonstrates a strong link between UVA-induced estrogen metabolism and increased susceptibility of females for FECD development.},
	issn = {1091-6490},
	doi = {10.1073/pnas.1912546116},
	author = {Liu, Cailing and Miyajima, Taiga and Melangath, Geetha and Miyai, Takashi and Vasanth, Shivakumar and Deshpande, Neha and Kumar, Varun and Ong Tone, Stephan and Gupta, Reena and Zhu, Shan and Vojnovic, Dijana and Chen, Yuming and Rogan, Eleanor G and Mondal, Bodhiswatta and Zahid, Muhammad and Jurkunas, Ula V}
}
