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Cailing Liu, Taiga Miyajima, Shivakumar Vasanth, Takashi Miyai, Bill Farinelli, Ula V. Jurkunas; N-Acetylcysteine Alleviates Progression of Fuchs Endothelial Corneal Dystrophy in a UVA Irradiation-Induced Mouse Model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1356.
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© ARVO (1962-2015); The Authors (2016-present)
Fuchs Endothelial Corneal Dystrophy (FECD) is a leading cause of corneal endothelial degeneration resulting in severe impairment of vision. We have established a UVA-induced mouse model that recapitulates FECD due to oxidative stress. 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.
Seven to nine week-old mice were irradiated with 1000 J/cm2 UVA in the right eyes, while the left eyes were used as no-UVA controls. Mice received pure drinking water or NAC drinking water at 1g/kg body weight until 3 months post UVA. 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. Aqueous humor (AH) was collected at 1 day post UVA and H2O2levels were evaluated with Amplex® Red assay. Mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage were evaluated using long-amplicon qPCR.
NAC-treated mice showed increased CEnC density at 2 months post UVA (1541± 225 cell/mm2) compared to UVA irradiated mice that did not receive NAC (900 ± 126 cell/mm2) (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). Moreover, treatment of NAC resulted in a 44% decrease in H2O2 level in the AH as compared to NAC-untreated eyes at 1 day post UVA irradiation (P < 0.05). UVA irradiation induced DNA damage in CEnCs by decreasing amplification of mtDNA by 51% and nDNA by 41% at a 3-month time point. 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. DNA damage was not prominent in male mice post UVA.
Administration of NAC rescues UVA-induced corneal edema, CEnC density, and DNA damage. NAC alleviates the pathological changes reminiscent of FECD and provides an in vivo evidence for therapeutic intervention.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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