Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Elevated Expression of Phospholipid Transfer Protein in Bone Marrow Derived Cells Causes Atherosclerosis

Background: Phospholipid transfer protein (PLTP) is expressed by various cell types. In plasma, it is associated with high density lipoproteins (HDL). Elevated levels of PLTP in transgenic mice result in decreased HDL and increased atherosclerosis. PLTP is present in human atherosclerosis lesions, where it seems to be macrophage derived. The aim of the present study is to evaluate the atherogenic potential of macrophage derived PLTP. Methods and Findings: Here we show that macrophages from human PLTP transgenic mice secrete active PLTP. Subsequently, we performed bone marrow transplantations using either wild type mice (PLTPwt/wt), hemizygous PLTP transgenic mice (huPLTPtg/wt) or homozygous PLTP transgenic mice (huPLTPtg/tg) as donors and low density lipoprotein receptor deficient mice (LDLR-/-) as acceptors, in order to establish the role of PLTP expressed by bone marrow derived cells in diet-induced atherogenesis. Atherosclerosis was increased in the huPLTPtg/wt → LDLR-/ - mice (2.3-fold) and even further in the huPLTPtg/tg→LDLR-/ - mice (4.5-fold) compared with the control PLTPwt/wt→LDLR-/- mice (both P<0.001). Plasma PLTP activity levels and non-HDL cholesterol were increased and HDL cholesterol decreased compared with controls (all P<0.01). PLTP was present in atherosclerotic plaques in the mice as demonstrated by immunohistochemistry and appears to co-localize with macrophages. Isolated macrophages from PLTP transgenic mice do not show differences in cholesterol efflux or in cytokine production. Lipopolysaccharide activation of macrophages results in increased production of PLTP. This effect was strongly amplified in PLTP transgenic macrophages. Conclusions: We conclude that PLTP expression by bone marrow derived cells results in atherogenic effects on plasma lipids, increased PLTP activity, high local PLTP protein levels in the atherosclerotic lesions and increased atherosclerotic lesion size

Twenty-four hours of insulin infusion does not lower plasma lipoprotein(a) in healthy men

The effect of 24-h exogenous hyperinsulinaemia on the plasma level of the atherogenic lipoprotein(a) (Lp(a)) is unknown. We evaluated the responses of plasma cholesterol, triglycerides, apolipoprotein (apo) B and Lp(a) during 24-h insulin infusion (180 pmol/kg/h) in 6 healthy men. Plasma total cholesterol (p <0.01) and triglycerides (p <0.05) decreased after 24 h of hyperinsulinaemia. Apo B was unchanged after 8 h (-2.4 +/- 3.0%, n.s.) and decreased by 10.9 +/- 4.8% (p <0.025) after 24 h of insulin. In contrast, Lp(a) did not decrease (+28.4 +/- 18.4%, n.s., and +49.1 +/- 22.0%, n.s., after 8 and 24 h of insulin, respectively). This experiment supports the hypothesis that moderate hyperinsulinaemia has a different effect on the plasma level of triglyceride-rich lipoproteins compared to Lp(a)

Twenty-four hours of insulin infusion does not lower plasma lipoprotein(a) in healthy men

The effect of 24-h exogenous hyperinsulinaemia on the plasma level of the atherogenic lipoprotein(a) (Lp(a)) is unknown. We evaluated the responses of plasma cholesterol, triglycerides, apolipoprotein (apo) B and Lp(a) during 24-h insulin infusion (180 pmol/kg/h) in 6 healthy men. Plasma total cholesterol (p <0.01) and triglycerides (p <0.05) decreased after 24 h of hyperinsulinaemia. Apo B was unchanged after 8 h (-2.4 +/- 3.0%, n.s.) and decreased by 10.9 +/- 4.8% (p <0.025) after 24 h of insulin. In contrast, Lp(a) did not decrease (+28.4 +/- 18.4%, n.s., and +49.1 +/- 22.0%, n.s., after 8 and 24 h of insulin, respectively). This experiment supports the hypothesis that moderate hyperinsulinaemia has a different effect on the plasma level of triglyceride-rich lipoproteins compared to Lp(a)