March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
The Effect of Desiccating Environmental Stress on Spdef Null Mice that Lack Conjunctival Goblet Cells
Author Affiliations & Notes
  • Christina K. Marko
    Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • Ann Tisdale
    Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • Sandra Spurr-Michaud
    Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • Ilene K. Gipson
    Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Christina K. Marko, None; Ann Tisdale, None; Sandra Spurr-Michaud, None; Ilene K. Gipson, None
  • Footnotes
    Support  NIH Grants R01 EY03306 and R01 EY03306-S1 (AARA) to IKG.
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 2329. doi:https://doi.org/
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      Christina K. Marko, Ann Tisdale, Sandra Spurr-Michaud, Ilene K. Gipson; The Effect of Desiccating Environmental Stress on Spdef Null Mice that Lack Conjunctival Goblet Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2329. doi: https://doi.org/.

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

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Abstract

Purpose: : Recent work from our laboratory has demonstrated that mice null for the sterile alpha motif pointed domain epithelia-specific transcription factor (SPDEF) lack conjunctival goblet cells, exhibit increased corneal fluorescein staining and tear volume, and have a gene expression pattern similar to that seen in dry eye with a downregulation in goblet cell gene products and an upregulation in epithelial differentiation and keratinization genes. Surprisingly, while Spdef -/- mice demonstrate signs of early dry eye syndrome, they lack a more severe dry eye phenotype. The purpose of this study was to determine if challenging Spdef -/- mice with desiccating environmental stress results in a more exacerbated dry eye phenotype.

Methods: : Age-matched Spdef -/- and wild type (WT) mice were exposed to desiccating environmental stress in a controlled environment chamber (CEC; 20.4 ± 0.5°C; 13.4 ± 2.9% relative humidity) for 15 days. Tear volume and corneal fluorescein staining were measured prior to entering the CEC and subsequently every 3 days. Animals were sacrificed and eyes with eyelids were excised, embedded, and sectioned to assess ocular surface histology and number of inflammatory cells in the cornea.

Results: : Exposure to desiccating stress induced increased tear volume in Spdef -/- mice as compared to non-stressed Spdef -/- and CEC-stressed WT mice. Additionally, tear volume in CEC Spdef -/- mice increased significantly with exposure time, while WT mice consistently had lower tear volumes. Corneal fluorescein staining score increased earlier after the onset of desiccating stress in Spdef -/- mice as compared to WT. An increase in the number of inflammatory cells in the cornea was observed in the CEC-exposed Spdef -/- mice as compared to CEC-exposed WT and unexposed Spdef -/- mice.

Conclusions: : Exposure to a dry environment exacerbates the early dry eye phenotype observed in Spdef -/- mice that lack conjunctival goblet cells. These data indicate that goblet cells and their products are important for protecting the ocular surface from environmental desiccating stress. The Spdef -/- mouse may be a new, more convenient dry eye model since scopolamine injections are not required to induce a dry eye phenotype.

Keywords: cornea: tears/tear film/dry eye • conjunctiva • cornea: surface mucins 
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