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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.
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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.
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.
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.
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.
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