The Dry Eye Zone

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Abstract: Desiccating stress and mucin deficiency

Entrapment of Conjunctival Goblet Cells by Desiccation-Induced Cornification.

Purpose:
To evaluate the effects of desiccating stress on conjunctival goblet cell density and morphology and expression of cornified envelope precursors by the ocular surface epithelia.

Methods:
Experimental dry eye (EDE) was created in C57BL/6 mice. Real time PCR evaluated the expression of cornified envelope (CE) precursor proteins (involucrin, small proline-rich [Sprr] protein 1a, 1b, 2a, 2b, 2f, and 2g), the cross-linking transglutaminase 1 enzyme (Tg-1) and Muc5AC mRNA transcripts by the ocular surface epithelia. Laser scanning confocal microscopy evaluated the expression of CE precursor proteins, Tg-1 and Muc5AC in cryosections. Tg-1 activity was measured by a fluorescein cadaverine assay. Muc5AC concentration was measured by ELISA.

Results:
Levels of involucrin, Sprr-1a, -1b, -2a, -2b, -2f, and -2g and Tg1-1 mRNA transcripts in ocular surface tissues increased in response to desiccating stress. Expression and activity of Tg in the conjunctiva markedly increased after EDE. Desiccating stress caused progressive loss of mucin-filled goblet cells. The apical portion of remaining conjunctival goblet cells became entrapped by adjacent stratified apical epithelia expressing increased levels of cornified envelope precursors.

Conclusions:
Exposure to desiccating stress stimulates ocular surface epithelia to produce of cornified envelope precursors and the tissue transglutaminase enzyme that cross links them. This is accompanied by loss of mucin-filled goblet cells and entrapment of mucin contents in remaining ones by cornifying cells that block egress of mucin contents to the ocular surface. This mechanism may contribute to the conjunctival mucin deficiency that develops in dry eye.

Invest Ophthalmol Vis Sci. 2011 Mar 18. [Epub ahead of print]
Corrales RM, de Paiva CS, Li DQ, Farley WJ, Henriksson JT, Bergmanson JP, Pflugfelder SC.
Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas;
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