title: Entrapment of conjunctival goblet cells by desiccation-induced cornification.
abstract: OBJECTIVE
  To evaluate the effects of desiccating stress on conjunctival goblet cell density and morphology and the 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 and small proline-rich [Sprr] -1a, -1b, -2a, -2b, -2f, and -2g proteins), 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 the 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 the 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 cornified envelope precursors and the tissue transglutaminase enzyme that cross-links them. This effect is accompanied by loss of mucin-filled goblet cells and entrapment of mucin contents in the remaining ones by cornifying cells that block the egress of mucin contents to the ocular surface. This mechanism may contribute to the conjunctival mucin deficiency that develops in dry eye.
authors.affiliation: Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas 77030, USA. corrales@bcm.edu
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Corrales
authors.forename: Cintia Sade
authors.initials: CS
authors.lastname: de Paiva
authors.forename: De-Quan
authors.initials: DQ
authors.lastname: Li
authors.forename: William Johnson
authors.initials: WJ
authors.lastname: Farley
authors.forename: Johanna Tukler
authors.initials: JT
authors.lastname: Henriksson
authors.forename: Jan Per Gustav
authors.initials: JP
authors.lastname: Bergmanson
authors.forename: Stephen Carl
authors.initials: SC
authors.lastname: Pflugfelder
mesh_terms: D000818:Animals; D002452:Cell Count; D003228:Conjunctiva / Q000378:metabolism / Q000473:pathology*; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics; D003890:Desiccation; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000502:physiology; D020397:Goblet Cells / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D055271:Mucin 5AC / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; C107162:TG-1 peptide; C032253:involucrin