Abstract
Purpose :
Fuchs endothelial corneal dystrophy (FECD) is a degenerative disease of the corneal endothelium (CE) with multiple and poorly understood etiologies. Hallmarks of FECD are corneal endothelial cell (CEnC) loss and endothelial guttata. Previously, we have reported that loss of antioxidant enzyme NQO1, which is transcriptionally regulated by Nrf2, and upregulation of estrogen metabolizing enzyme CYP1B1 contribute to increased susceptibility of CEnCs to ultraviolet-A (UVA) light, a physiologic stressor of CE. The purpose of this study is to test the protective effect of a naturally occurring Nrf2 agonist and CYP1B1 inhibitor, berberine, against CEnC loss after UVA exposure in vivo.
Methods :
10-week-old C57BL/6 female mice corneas were irradiated with UVA light (500 J/cm2). Post-irradiation, 2 cohorts of mice (N=5 each) were intraperitoneally injected with 10 mg/kg berberine or vehicle once a week up to 1 month. CEnCs were imaged before and at 1 week, 2 weeks, and 1-month post-UVA using Heidelberg Retinal Imaging Rostock Corneal Module (HRT-RCM). Cell counting was performed using ImageJ and statistical analyses of computed cell density were performed using a one-way analysis of variance (ANOVA) and post-hoc Tukey’s HSD.
Results :
At 1-week post-UVA, the vehicle-treated group showed a 25.3±2.7% decrease (1760±23 vs. 2362±42 cells/mm2 at baseline; p<0.001), while the berberine-treated group showed only a 12.7±1.4% decrease (1970±28 vs. 2263±64 cells/mm2 at baseline; p<0.001) in CEnC density, thus exhibiting 49% protection with drug compared to no treatment (p<0.01). At 2 weeks, the vehicle-treated group showed a 37.5±2.7% decrease (1474±49 vs. 2362±42 cells/mm2 at baseline; p<0.001), whereas the berberine-treated group showed only a 19.4±1.4% decrease (1822±27 vs. 2263±64 cells/mm2 at baseline; p<0.001) in CEnC density, indicating a continued 48% protection with drug compared to no treatment (p<0.001) at this time-point.
Conclusions :
We demonstrate that treatment with berberine can rescue UVA-mediated CEnC loss at an early time-point in FECD. This study provides a potential line of treatment to rescue a deficient antioxidant system in FECD. Further investigation into the long term effect is warranted.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.