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Ilene Gipson, Albert Alhatem, Gang Chen, Jeffrey Whitsett, Hans Clever; The Role of the Transcription Factor SPDEF in Goblet Cell Differentiation in the Conjunctiva. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2584. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Little is known regarding differentiation of goblet cells in the conjunctival epithelium. Mice null for the SAM (sterile alpha motif) pointed domain epithelia specific transcription factor (SPDEF) lack goblet cells in tracheobronchial epithelia. The purpose of this study was to determine if SPDEF regulates goblet cell differentiation in the conjunctiva.
Conjunctival tissue from mice null for SPDEF were examined by light microscopy for presence of goblet cells, the ocular surface of the mice was examined by fluorescein staining for surface changes, and tear volume was measured by cotton thread test. SPDEF was localized in human and mouse conjunctival epithelium by immunohistochemistry. The amount of SPDEF mRNA in conjunctival biopsies from patients with Sjögren’s Dry Eye with documented downregulation of the goblet cell mucin MUC5AC was compared to that of normal conjunctiva using real-time PCR.
Conjunctival epithelia of SPDEF -/- mice lacked goblet cells and occasional inflammatory cells were present in SPDEF -/- epithelium. There was no obvious corneal or eyelid phenotype in the null mice, and there was no fluorescein staining of the ocular surface. Tear fluid levels were, however, significantly increased. SPDEF protein was localized in conjunctival goblet cell nuclei by immunohistochemistry in both human and mouse conjunctival epithelium. A significant decrease in SPDEF mRNA was found in conjunctival epithelial samples from patients with dry eye resulting from Sjögren’s Syndrome as compared to that from normal subjects. These data are opposite that found in tracheal epithelial disease where chronic inflammation leads to goblet cell proliferation in response to increased SPDEF expression.
Taken together these data indicate that SPDEF is involved in regulation of goblet cell differentiation in the conjunctiva, but goblet cell differentiation in the conjunctival epithelium in response to chronic inflammation differs from that of the tracheal epithelium.
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