June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Characterization of the cornea in the YAP-/+ mouse
Author Affiliations & Notes
  • Soohyun Kim
    Veterinary Surgical and Radiological Science, University of California Davis, Davis, California, United States
  • Sara M Thomasy
    Veterinary Surgical and Radiological Science, University of California Davis, Davis, California, United States
  • Vijay Krishna Raghunathan
    The Ocular Surface Institute, College of Optometry, University of Houston, Houston, Texas, United States
  • Paul G FitzGerald
    Department of Cell Biology and Human Anatomy, School of Medicine, University of California Davis, Davis, California, United States
  • Christopher J Murphy
    Veterinary Surgical and Radiological Science, University of California Davis, Davis, California, United States
    Department of Ophthalmology & Vision Science, School of Medicine, University of California Davis, Davis, California, United States
  • Footnotes
    Commercial Relationships   Soohyun Kim, None; Sara Thomasy, None; Vijay Raghunathan, None; Paul FitzGerald, None; Christopher Murphy, None
  • Footnotes
    Support  NIH Grant K08 EY021142, R01 EY019970, R01 EY016134, and P30 EY12576
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1418. doi:
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    • Get Citation

      Soohyun Kim, Sara M Thomasy, Vijay Krishna Raghunathan, Paul G FitzGerald, Christopher J Murphy; Characterization of the cornea in the YAP-/+ mouse. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1418.

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

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Abstract

Purpose : Yes-associated protein (YAP), is a transcriptional co-activator encoded by the gene YAP, is part of the Hippo pathway and has critical functions in cell proliferation, apoptosis and mechanotransduction. Homozygous deletion of the YAP gene is known to be embryonic lethal and its dysregulation has been implicated in developmental abnormalities, such as hydrocephalus and renal disease. The purpose of this study was to identify the cornea phenotypic consequences of a single copy deletion of YAP (YAP-/+) in the mouse cornea.

Methods : Male YAP-/+ mice were generated on a C57BL/6N background and breed to wildtype (WT) females on a C57BL/6J background. 318 pups were genotyped with PCR. Complete ophthalmic examination (slit lamp and indirect ophthalmoscopy) with digital photography as well as corneal aesthesiometry, phenol red thread test, intraocular pressure, and OCT, were performed on 18 mice between 14 days after birth (eyelid opening) and 9-month-old. Findings were compared between YAP-/+ and age-matched WT. Following euthanasia, enucleated eyes were fixed using freeze substitution and processed for histological characterization.

Results : Microphthalmia with small palpebral fissures, corneal fibrosis and reduced corneal sensation were common findings in YAP-/+ mice. Generalized corneal fibrosis precluded clinical examination of posterior structures. Corneal thickness of the YAP-/+ mouse was thinner than the WT as determined by OCT. Histologically, thinning of corneal epithelium was observed in YAP-/+ mice in comparison with WT and lacked the normal morphology of a stratified squamous epithelial layer. Distorted stromal fiber arrangement and edema were observed with stromal blood vessels. Descemet’s membrane was not observed in many YAP-/+ mice, and in cases when present, was extremely thin and lacked an endothelial layer. The iris was adherent to the posterior cornea along most of its surface creating a distorted contour. Most of the YAP-/+ eyes lacked identifiable lenses or were extremely microphakic with swollen fibers and/or bladder cells.

Conclusions : Our results show that the heterozygous deletion of the YAP gene in mice leads to the loss of corneal transparency due to the fibrosis, neovascularization, edema and abnormal endothelial structures with microphthalmia and lens abnormalities.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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