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