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

High‐Resolution P‐T‐Time Paths Across Himalayan Faults Exposed Along the Bhagirathi Transect NW India: Implications for the Construction of the Himalayan Orogen and Ongoing Deformation

Abstract Pressure‐temperature (P‐T) conditions and high‐resolution paths from 11 garnet‐bearing rocks collected across Himalayan fault systems exposed along the Bhagirathi River (Uttarakhand, NW India) reveal the tectonic conditions responsible for their growth. A garnet from the Tethyan metasedimentary unit has a 50.3 ± 0.6 Ma (Th‐Pb, ±1σ) monazite inclusion, suggesting that ductile mid‐crustal metamorphism occurred synchronously or soon after (<10 Myr) India‐Asia collision, depending on timing. High‐resolution garnet P‐T paths from the same rock show ∼1 kbar fluctuations in P as T increases over a ∼20°C interval, consistent with a period of erosion. We report garnets from the Main Central Thrust (MCT) hanging wall that have Eocene to Miocene monazite ages, and one garnet yields paths consistent with motion along the Main Himalayan Thrust (MHT) décollement. Most high‐resolution MCT footwall P‐T paths fluctuate in P (±1 kbar) as T increases, consistent with imbrication and paths from equivalent structural assemblages in central Nepal. Like those rocks, MCT footwall (Lesser Himalayan Formation, LHF) monazite ages are Early Miocene (9.3 ± 0.6 Ma) to Pliocene (3.0 ± 0.2 Ma). The results demonstrate the consistency in timing and conditions across the MCT at locations ∼650 km apart. If the present‐day Himalayan tectonic framework has not significantly changed since the Pliocene, the LHF duplex can be considered when attributing seismic events to particular faults. The MHT is undisputedly the significant factor in accommodating Himalayan seismic activity, but MCT footwall faults may explain some shallower hypocenters, without the need for unusual MHT geometries