NAC alleviates the pathological changes reminiscent of FECD and provides an in vivo evidence for therapeutic intervention. DNA damage was not prominent in male mice post UVA.Īdministration of NAC rescues UVA-induced corneal edema, CEnC density, and DNA damage. However, NAC treatment increased mtDNA amplification by 15% and nDNA amplification by 58% compared to NAC untreated mice, specifically in females at 3 months post UVA. UVA irradiation induced DNA damage in CEnCs by decreasing amplification of mtDNA by 51% and nDNA by 41% at a 3-month time point. Moreover, treatment of NAC resulted in a 44% decrease in H 2O 2 level in the AH as compared to NAC-untreated eyes at 1 day post UVA irradiation (P < 0.05). Administration of NAC decreased CCT (112 ± 5 μm in males and 105 ± 12 μm in females), compared to NAC untreated mice (144 ± 9 μm in males and 166 ± 8 μm in females) at 3 months post UVA (P < 0.05). NAC-treated mice showed increased CEnC density at 2 months post UVA (1541± 225 cell/mm 2) compared to UVA irradiated mice that did not receive NAC (900 ± 126 cell/mm 2) (P < 0.05). Mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage were evaluated using long-amplicon qPCR.
Aqueous humor (AH) was collected at 1 day post UVA and H 2O 2levels were evaluated with Amplex® Red assay. Mouse corneal endothelial cell (CEnC) morphology and density were examined by HRT and corneal thickness (CCT) was measured by OCT at 1d, 1wk, 2 wk, 1 mo, 2 mo and 3 mo post UVA irradiation. Mice received pure drinking water or NAC drinking water at 1g/kg body weight until 3 months post UVA. Seven to nine week-old mice were irradiated with 1000 J/cm 2 UVA in the right eyes, while the left eyes were used as no-UVA controls. In this study, we aimed to investigate the effect of N-acetylcysteine (NAC), a scavenger of reactive oxygen species (ROS), in alleviating the clinical outcomes and molecular pathogenesis induced by UVA in this mouse model of FECD. We have established a UVA-induced mouse model that recapitulates FECD due to oxidative stress. Fuchs Endothelial Corneal Dystrophy (FECD) is a leading cause of corneal endothelial degeneration resulting in severe impairment of vision.
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