Predictive molecular profiling in blood of healthy vasospastic individuals: clue to targeted prevention as personalised medicine to effective costs

Abstract

Paradigm change from late interventional approach to predictive diagnostics followed by targeted prevention before manifest pathology, presents innovative concept for advanced healthcare. Preselection of healthy but pathology-predisposed individuals is the primary task in the overall action. Vasospasm is a frequent syndrome defined as an inappropriate constriction or insufficient dilatation in microcirculation. Vasospastic individuals are considered as healthy subpopulation predisposed to several pathologies including neurodegeneration. Clinical observations, subcellular imaging and "gene hunting"-investigations provide evidence for vasospasm as predisposition to glaucoma; development of further related pathologies cannot be excluded. Predictive molecular-profiling in blood can specify individual predisposition for effective prevention.

Fig. 1

Alterations in conjunctival vessels in patients with vasospasm [1]

Fig. 2

Nailfold capillary microscopy (right) enables the monitoring of microcirculation and cold provocation of vasospasm in fingers (left) [1]

Fig. 3

Ex vivo “Comet Assay”-analysis of DNA damage in circulating leucocytes of glaucoma patients and non-glaucomatous vasospastic individuals versus healthy controls [19]. Figures A–D give examples of images typical for a. control group, b. group of vasospastic individuals, c. group of normal-tension glaucoma patients, and d. group of high-tension glaucoma patients. Comet-patterns typical for healthy controls (A) show that chromosomal DNA is localised mainly to heads of comets (intact DNA). In contrast, images B, C, and D demonstrate clearly damaged DNA (visible comet-tails and diffuse comet-heads). Evaluation of the shape of a comet allows for assessment of DNA damage. Individual migration patterns are demonstrated in groups corresponding to the images A–D by the evaluation of comet-classes (class number progression corresponds to increasing damage degree) as described earlier [20]. Figure E shows mean values calculated for relative DNA damage in following groups as compared to the control group (100%): VI—vasospastic individuals (102 ± 7%), NTG normal-tension glaucoma (160 ± 13%), and HTG high-tension glaucoma (128 ± 10%) [18]

Fig. 4

Proteomics-imaging of blood-biomarkers (ex vivo identification in circulating leucocytes) specific for normal-tension glaucoma (NTG). A. Top: The pathology-specific protein-cluster is completely suppressed in both NTG and vasospasm in contrast to controls. B. Bottom: The marked protein SSP2602 is highly up-regulated in both NTG and vasospasm; this protein normally is not expressed by circulating leucocytes of controls—healthy individuals without vasospasm [22]