July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
A novel mouse model carrying a mutation in Gsdma3 resembles late stage Evaporative Dry Eye (EDE) disease and presents with alopecia and corneal inflammation.
Author Affiliations & Notes
  • John Per Neidhardt
    Human Genetics, University of Oldenburg, Oldenburg, Germany
    Research Center Neurosensory Science, University Oldenburg, Oldenburg, Germany
  • Carsten Röger
    Human Genetics, University of Oldenburg, Oldenburg, Germany
  • Aldona Pienkowska-Schelling
    Institute of Genetics, University of Bern, Bern, Switzerland
  • Cynthia Ihlenburg
    Institut für Pathologie , Wilhelmshaven, Germany
  • Gösta Fischer
    Institut für Pathologie , Wilhelmshaven, Germany
  • Oliver May
    Human Genetics, University of Oldenburg, Oldenburg, Germany
  • Mariann Vorm
    Human Genetics, University of Oldenburg, Oldenburg, Germany
  • Marta Owczarek-Lipska
    Human Genetics, University of Oldenburg, Oldenburg, Germany
  • Sebastian Swirski
    Human Genetics, University of Oldenburg, Oldenburg, Germany
  • Footnotes
    Commercial Relationships   John Neidhardt, None; Carsten Röger, None; Aldona Pienkowska-Schelling, None; Cynthia Ihlenburg, None; Gösta Fischer, None; Oliver May, None; Mariann Vorm, None; Marta Owczarek-Lipska, None; Sebastian Swirski, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2275. doi:
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      John Per Neidhardt, Carsten Röger, Aldona Pienkowska-Schelling, Cynthia Ihlenburg, Gösta Fischer, Oliver May, Mariann Vorm, Marta Owczarek-Lipska, Sebastian Swirski; A novel mouse model carrying a mutation in Gsdma3 resembles late stage Evaporative Dry Eye (EDE) disease and presents with alopecia and corneal inflammation.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2275.

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

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Abstract

Purpose : Mutations in the mouse gene Gasdermin A3 (Gsdma3) frequently lead to severe skin phenotypes. We discovered a novel C-terminal mutation in Gsdma3 in a new mouse line that additionally shows a corneal phenotype which likely is caused by degeneration of Meibomian glands of the inner eye lid.

Methods : We used histological methods to evaluate the effects of the new Gsdma3 mutation on sebaceous gland and skin morphology as well as Meibomian glands of the inner eye lid and corneal tissue. The mutation was identified by Sanger sequencing of candidate genes. Chromosomal aberrations were excluded by karyogram analyses. Immunohistological techniques were used to detect laminin and CD3 positive cells in the cornea.

Results : The occurrence of phenotypes in the new mouse model (C+/H-) followed an autosomal dominant inheritance pattern. Histological analyses of skin samples from affected mice confirmed the previously reported degeneration of sebaceous glands and a complete loss of pelage. Additionally, a corneal phenotype was observed at irregular time points and often started at around 6 months of age. Its appearance coincided with a degeneration of Meibomian glands that presented with reduced lipid contend. The corneal alterations started with corneal opacity. In later stages the central part of the cornea developed an increase of tissue that progressed until the eye closure was impaired. Histological analyses showed an increase in size of the stromal layer and suggested corneal neovascularization, observations that were complemented by immunological staining showing increased laminin signals and the appearance of CD3-positive T-cells in affected corneas.

Conclusions : The mutation described herein leads to inflammation and neovascularization of corneal tissue. Concurrent degeneration of Meibomian glands in affected animals suggested a change in tear-film composition as the underlying cause for the corneal phenotype. Our data further support that different pathogenic mechanisms underlie some of the reported mutations in Gsdma3. The new mouse model reported here may serve as a disease model for late stage EDE.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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