N-Acetylcysteine increases corneal endothelial cell survival in a mouse model of Fuchs endothelial corneal dystrophy.

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The present study evaluated survival effects of N-acetylcysteine (NAC ) on cultured corneal endothelial cells exposed to oxidative and endoplasmic reticulum (ER ) stress and in a mouse model of early -onset Fuchs endothelial corneal dystrophy (FECD ). Cultured bovine corneal endothelial cell viability against oxidative and ER stress was determined by CellTiter-Glo (®) luminescent reagent . Two -month -old homozygous knock-in Col 8 a 2 (L 450 W /L 450 W ) mutant (L 450 W ) and C 5 7 /Bl 6 wild-type (WT ) animals were divided into two groups of 15 mice . Group I received 7 mg /mL NAC in drinking water and Group II received control water for 7 months . Endothelial cell density and morphology were evaluated with confocal microscopy . Antioxidant gene (iNos ) and ER stress /unfolded protein response gene (Grp 78 and Chop ) mRNA levels and protein expression were measured in corneal endothelium by real time PCR and Western blotting . Cell viability of H 2 O 2 and thapsigargin exposed cells pre-treated with NAC was significantly increased compared to untreated controls (p < 0 .01 ). Corneal endothelial cell density (CD ) was higher (p = 0 .001 ) and percent polymegathism was lower (p = 0 .04 ) in NAC treated L 450 W mice than in untreated L 450 W mice . NAC treated L 450 W endothelium showed significant upregulation of iNos , whereas Grp 78 and Chop were downregulated compared to untreated L 450 W endothelium by real time PCR and Western blotting . NAC increases survival in cultured corneal endothelial cells exposed against ER and oxidative stress . Systemic NAC ingestion increases corneal endothelial cell survival which is associated with increased antioxidant and decreased ER stress markers in a mouse model of early -onset FECD . Our study presents in vivo evidence of a novel potential medical treatment for FECD .