July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
The phenotype of knock-out mouse of tumor-associated calcium signal transducer2 as a model of gelatinous drop-like corneal dystrophy
Author Affiliations & Notes
  • Yukiko Nagahara
    Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan
  • koji uesugi
    Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan
  • Peng Xu
    Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan
  • Satoshi Kawasaki
    Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan
  • Motokazu Tsujikawa
    Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan
  • Kohji Nishida
    Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan
  • Footnotes
    Commercial Relationships   Yukiko Nagahara, None; koji uesugi, None; Peng Xu, None; Satoshi Kawasaki, None; Motokazu Tsujikawa, None; Kohji Nishida, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2970. doi:
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      Yukiko Nagahara, koji uesugi, Peng Xu, Satoshi Kawasaki, Motokazu Tsujikawa, Kohji Nishida; The phenotype of knock-out mouse of tumor-associated calcium signal transducer2 as a model of gelatinous drop-like corneal dystrophy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2970.

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

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Abstract

Purpose : Gelatinous drop-like corneal dystrophy (GDLD) is one of the severest inherited corneal diseases. We made a conventional knock-out mouse of tumor-associated calcium signal transducer2 (TACSTD2) which is a causative gene of GDLD. The phenotype of corneal opacity and delayed stained and tight junction were analyzed and the pathogenicity was examined.

Methods : The mouse born normally and there was no significant phenotype. The phenotypes of human GDLD in the eye are late-onset and progressive opacity. First, we analyzed the phenotype of corneal opacity in older mice. The presence or absence of corneal opacity lesions of all 34 eyes (Tacstd2 -/- 16 eyes, Tacstd2 +/+ 18 eyes) that passed more than a year and a half after birth were confirmed and the relationship between genotype and turbidity was investigated. Second, to test the increased corneal permeability, we confirmed delayed stained of cornea in young mice (6 weeks) without turbidity. fluorescein (0.3%) was dropped and washed after 3 minutes with 50ml water. The stained area was measured. Third, we checked the tight junction of corneal epithelium in young mice (4 weeks) with a transmission electron microscope. The state of adhesion between corneal epithelial cells on the apical side was observed.

Results : We confirmed that mouse TACSTD2 gene was not expressed by RT-PCR using the tissue of cornea in Tacstd2 -/- mouse. The phenotype of corneal opacity was defined severe as enough to cover the pupil area and defined mild as less opacity by judging an independent examiner. The turbidity was strongly correlated with the genotype (p=2.60×10-5). Corneal angiogenesis and kumquat like opacity were also observed in some Tacstd2 -/- mice. Delayed stain, which was vulnerable to corneal epithelial barrier function was significantly observed in Tacstd2 -/-mice (p <1.0×10 -4). A number of tight junctions of the corneal epithelium in Tacstd2 -/- mice had disappeared significantly (p <1.0×10 -4).

Conclusions : Tacstd2 -/- mice showed phenotypes similar to that of human GDLD. The mouse is a strong tool in investigating the pathology of GDLD and developing new therapy.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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