June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
A new model for endothelial injury in TAZ deficient mice using phototherapeutic keratectomy
Author Affiliations & Notes
  • Sangwan Park
    Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, United States
  • Brian Leonard
    Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, United States
  • Soohyun Kim
    Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, United States
  • Michelle Emily Mccorkell
    Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, United States
  • Christopher Murphy
    Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, United States
    Department of Ophthalmology and Vision Science, School of Medicine, University of California Davis, Davis, California, United States
  • Vijaykrishna Raghunathan
    The Ocular Surface Institute, College of Optometry, University of Houston, Houston, Texas, United States
    Department of Biomedical Engineering, Cullen College of Engineering, University of Houston, Houston, Texas, United States
  • Sara M Thomasy
    Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, United States
    Department of Ophthalmology and Vision Science, School of Medicine, University of California Davis, Davis, California, United States
  • Footnotes
    Commercial Relationships   Sangwan Park, None; Brian Leonard, None; Soohyun Kim, None; Michelle Mccorkell, None; Christopher Murphy, None; Vijaykrishna Raghunathan, None; Sara Thomasy, None
  • Footnotes
    Support  R01EY019970, 2R01EY016134, P30EY12576, K08EY028199, R01EY016134, P30EY12576
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1475. doi:
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    • Get Citation

      Sangwan Park, Brian Leonard, Soohyun Kim, Michelle Emily Mccorkell, Christopher Murphy, Vijaykrishna Raghunathan, Sara M Thomasy; A new model for endothelial injury in TAZ deficient mice using phototherapeutic keratectomy. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1475.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Mice deficient in Wwtr1, the gene that encodes transcriptional co-activator with PDZ-binding motif (TAZ) are associated with decreased corneal endothelial cell (CEnC) density and alteration in Descemet’s membrane reminiscent of late-onset Fuchs’ endothelial dystrophy. The purpose of this study was to evaluate the regenerative capacity of CEnCs following excimer laser-induced injury in TAZ deficient (Wwtr1+/-) and wildtype (WT) mice.

Methods : A phototherapeutic keratectomy (PTK) was performed with an excimer laser (2 mm diameter, 40 Hz, 20 μm depth) in both eyes of 6-month-old Wwtr1+/- and WT mice (N=6 for each genotype). Prior to PTK and on postoperative days 1, 3, 5, 7, 10 and 14, slit lamp biomicroscopy, Fourier-domain optical coherence tomography and in vivo confocal microscopy (IVCM) were performed to monitor clinical progression, central corneal thickness (CCT) and CEnC density, respectively. Following euthanasia on day 14, corneas were excised and stained with Alizarin red and zonula occludens-1 (ZO-1) to evaluate CEnC density and morphology.

Results : Prior to PTK, there were no statistical difference in CCT and CEnC density between WT and Wwtr1+/- mice at 89 ± 10.2 μm and 2668 ± 208 cells/mm2 versus 99 ± 6.7 μm and 2485 ± 133 cells/mm2, respectively. Following PTK, corneal edema and an associated increase in CCT were observed which peaked on day 7 in WT (125 ± 14.4 μm) and day 10 in Wwtr1+/- (141 ± 32.5 μm) but returned to baseline on day 14 in both genotypes. There was no statistical difference in CCT between each genotype at all timepoints. On day 14, CEnC density was decreased from baseline values in both genotypes with IVCM and was significantly lower in Wwtr1+/- (1017 ± 302 cells/mm2, P < 0.05) versus WT mice (1592 ± 333 cells/mm2) with Alizarin red staining. The ZO-1 expression was more reduced in Wwtr1+/- versus WT mice.

Conclusions : Regeneration of CEnCs was significantly delayed in Wwtr1+/- mice following PTK-induced injury, suggesting that Wwtr1 may be crucial to CEnC regeneration. Further, we speculate that this model may be useful to evaluate novel medical therapies for CEnC regeneration.

This is a 2020 ARVO Annual Meeting abstract.

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