title: Dry eye symptoms are increased in mice deficient in phospholipid transfer protein (PLTP).
abstract: In the tear fluid the outermost part facing the tear-air interface is composed of lipids preventing evaporation of the tears. Phospholipid transfer protein (PLTP) mediates phospholipid transfer processes between serum lipoproteins and is also a normal component of human tears. To study whether PLTP plays any functional role in tear fluid we investigated PLTP-deficient mice, applying functional and morphologic analyses under normal housing and experimentally induced dry eye conditions. Aqueous tear fluid production, corneal epithelial morphology, barrier function, and occludin expression were assessed. In mice with a full deficiency of functional PLTP enhanced corneal epithelial damage, increased corneal permeability to carboxyfluorescein, and decreased corneal epithelial occludin expression were shown. These pathologic signs were worsened by experimentally induced dry eye both in wild-type and PLTP knock-out mice. Deficiency in the production of tear PLTP in mice is accompanied by corneal epithelial damage, a feature that is typical in human dry eye syndrome (DES). To complement animal experiments we collected tear fluid from human dry eye patients as well as healthy control subjects. Increased tear fluid PLTP activity was observed among DES patients. In conclusion, the presence of PLTP in tear fluid appears to be essential for maintaining a healthy and functional ocular surface. Increased PLTP activity in human tear fluid in DES patients suggests an ocular surface protective role for this lipid transfer protein.
authors.affiliation: Department of Ophthalmology, University of Helsinki, Helsinki, Finland.
authors.forename: Niko L
authors.initials: NL
authors.lastname: Setälä
authors.forename: Jari
authors.initials: J
authors.lastname: Metso
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Antti
authors.initials: A
authors.lastname: Sajantila
authors.forename: Juha M
authors.initials: JM
authors.lastname: Holopainen
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D002463:Cell Membrane Permeability / Q000502:physiology; D015352:Dry Eye Syndromes / Q000378:metabolism* / Q000473:pathology; D019573:Epithelium, Corneal / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D049294:Phospholipid Transfer Proteins / Q000172:deficiency / Q000378:metabolism*; D013666:Tears / Q000737:chemistry / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism
chemical_list: C493430:PLTP protein, human; D049294:Phospholipid Transfer Proteins; C510091:phospholipid transfer protein, mouse