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 PLTPdeficient 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. Dry eye syndrome (DES) is a multifactorial disease of the ocular surface. DES is accompanied by tear film instability, 1 increased osmolarity, 2,3 inflammation of the ocular surface, 4 and abnormalities in tear fluid components, especially lipids.5 Together these may lead to ocular surface damage. 6 The conventional structure of the tear film consists of three layers: a superficial lipid layer, an aqueous middle layer, and a precorneal mucin layer.7,8 It appears, however, that the two latter compartments form a somewhat homogenous gel-like and mucin-enriched fluid.9,10 The superficial lipid layer is a complex mixture of polar and nonpolar lipids arranged into a layered structure. Based on the hydrophobic effect it has been suggested that the polar phospholipids are aligned adjacent to the aqueous-mucin layer and externally to this a layer composed of nonpolar lipids, such as cholesteryl esters and triglycerides, face the tear-air interface. 8,11,12 The chemical composition and comprehensive lipid analysis of tear fluid have yet to be revealed. It is, however, clear that an imbalance of lipid layer in the tear fluid is involved intimately in the pathogenesis of DES.Similarly to cellular membranes 13 the tear fluid lipid layer is by no means a static lipid membrane. A diminished amount of certain lipids increases the evaporation rate and excess lipids cause thickening and packing difficulties in the air-tear interface leading to formation of lipid aggregates in the tear fluid. Because of the properties of ...

The Effect of Phospholipids on Tear Film Lipid Layer Surface Activity

“…The function of PLs may be highly affected by lipid-binding proteins such as lipocalin, [24][25][26] and PL transfer protein. 27,28 However, more investigations need to be performed regarding the lipid-protein interactions before the impact of the proteins on TFLL behavior can be explained in more detail.…”