Purchase this article with an account.
Cailing Liu, Takashi Miyai, Dijana Vojnovic, Irene E Kochevar, Ula V Jurkunas; UV-A Irradiation Induced Mouse Model of Fuchs Endothelial Corneal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Fuchs Endothelial Corneal Dystrophy (FECD) is characterized by progressive loss of corneal endothelial cells (CEnC) via apoptosis and guttae formation. Oxidative stress has been identified as one of the contributors to the FECD pathogenesis. In this study, we aimed to establish an in vivo model of late-onset and age-related FECD by inducing oxidative stress via UV-A irradiation of mouse CEnCs (MCEnCs).
Eyes of 7-15 wk-old female C57BL/6J mice were irradiated with UV-A with a single fluence of 250 J/cm2, 500 J/cm2, 750 J/cm2 or 1000 J/cm2. MCEnC morphology and density were examined by HRT and corneal thickness (CCT) was measured by OCT at 16 h, 48 h, 72 h, 1wk, 2 wk, 1 mo, 2 mo, and 3 mo post UV-A irradiation. Contralateral eyes without UV-A irradiation served as controls. Corneal whole mounts from UVA-irradiated and control eyes were analyzed with anti-ZO-1 antibody and TUNEL staining.
UV-A irradiation caused progressive morphological changes and loss of regular hexagonal shape in MCEnCs in a time- and dose- dependent manner. Specifically, HRT revealed dark areas of lost MCEnCs surrounded by disrupted cell boundaries, suggestive of findings observed in FECD patients. Irradiation with 250, 500, 750 and 1000 J/cm2 of UV-A led to a reduction in MCEnC density by 27.6 %, 79.4 %, 85.0 % and 88.5 %, respectively, as compared to control eyes 3 mo post irradiation. Furthermore, UV-A led to an acute increase in CCT that peaked at 48 h in mice irradiated with 500, 750, and 1000 J/cm2 (73.3 ± 33.7 %, 64.3 ± 2.96 %, 67.3 ± 13.6 % respectively; P < 0.05). CCT recovered between 7-60 days post UV-A, but exhibited a second wave of increase at 2 months post UV-A, indicating a chronic phase of endothelial dysfunction. ZO-1 staining revealed greater levels of cell boundary loss and cell size variation in edematous corneas at 3 months post UV-A. Additionally, TUNEL staining revealed apoptosis in UV-A treated cells.
Exposure of mouse corneas to UV-A resulted in a progressive loss of MCEnC hexagonal shape, a decrease in cell density, and an increase in CCT. Specifically, dark areas surrounded by irregular cell boundaries were indicative of morphological changes observed in FECD. This study provides the first animal model for studying the role of oxidative stress in late-onset and age-related FECD.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
This PDF is available to Subscribers Only