Genotype, Age, Genetic Background, and Sex Influence <i>Epha2</i>-Related Cataract Development in Mice

Purpose: Age-related cataract is the leading cause of blindness worldwide. Variants in EPHA2 gene increase disease risk, and its knockout mice causes cataract. We investigated whether age, sex, genetic background, risk factors for age-related cataract, Epha2 genotype influence Epha2-related development mice. Methods: Cataract was monitored Epha2+/+, Epha2+/−, Epha2−/− (Epha2Gt(KST085)Byg) on C57BL/6J FVB:C57BL/6J (50:50) backgrounds. Cellular architecture lenses, endoplasmic reticulum (ER) stress, redox state were determined using histological, molecular, analytical techniques. Results: Epha2+/− background developed severe cortical cataracts by 18 38 weeks respectively, compared to similar significantly later no this strain FVB which previously reported. On exhibited mild up 64 age. Progression female mixed slower than matched male N-cadherin β-catenin immunolabeling showed disorganized lens fiber cells disruption coinciding with cataracts. intracellular accumulation mutant EPHA2-β-galactosidase fusion protein that induced a cytoprotective ER stress response lenses also accompanied glutathione imbalance. Conclusions: Both, develop cataract; age as function genotype, cataractogenesis