What is it about?

Metabolomics has been widely used to assess biological systems, providing molecular information related to phenotype since metabolites are ultimate product of gene, mRNA and protein activity. There is a growing number of metabolomics applications aiming to identify biomarkers for accurate diagnosis, providing therapy guidance and assessing therapy response. Monitoring biomarker levels in biological systems could greatly assist in detecting the early stages of disease development with improved sensitivity.

Featured Image

Why is it important?

The main analytical techniques adopted in global metabolomics analysis are nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). MS was usually hyphenated with different separation techniques, such as liquid chromatography (LC-MS) [6], gas chromatography (GC-MS) and capillary electrophoresis (CE-MS), to enhance sensitivity. CE coupled to other detectors, such as ultraviolet-laser induced fluorescence (UV-LIF) and UV, and Fourier transform-infrared (FT-IR) spectroscopy are less commonly used. The proton is the most commonly-studied nucleus for NMR studies. While NMR is a non-destructive technique requiring minimal sample preparation, even allowing for the analysis of intact tissue, sensitivity and metabolite resolution in NMR are limited compared to GC-MS or LC-MS. Hyphenated techniques combining separation and mass spectrometry-based (MS) detection are increasingly adopted as the analytical platform of choice in metabolomics studies. The proportion of published metabolomics studies with mentions of “GC-MS” or “LC-MS” (including LC-MS/MS) in their titles or abstracts has doubled over the past decade. GC-MS and LC-MS-based metabolomics studies may be performed using untargeted (global) or targeted strategies. In untargeted studies, prior knowledge of metabolites of interest is not essential as full scan MS data is acquired. Tandem MS (MS/MS) data for metabolite identification may be acquired in the same analysis with data-dependent acquisition (DDA, also known as information dependent acquisition), or in separate analyses. Following peak detection and alignment, and statistical analysis of full scan data, marker metabolites are putatively identified by accurate mass searches in metabolite databases, and confirmed by comparison of their retention time and MS/MS spectra with pure standards. In contrast, targeted studies are set up to analyze only specified metabolites. This is typically performed using multiple-reaction-monitoring (MRM) or neutral-loss (NL) scans on triple quadrupole or ion trap mass spectrometers. A comprehensive listing of mass spectra databases has also been published recently .

Perspectives

With the improvement of metabolomics techniques, metabolic profiling has shed a light on the metabolism of normal ocular samples and disease pathogenesis. The emerging field of application of metabolomics in eye research has great potential for biomarker discovery in disease diagnosis. In this review, we have discussed recent advances of metabolomics analysis in eye research, with emphasis on ocular diseases. As shown from the above cited studies, ocular biofluids (aqueous humor, vitreous humor and tears) and tissue samples are valuable biological matrices in studying ocular diseases. Plasma and serum metabolite associations have been found for AMD, DR and glaucoma, opening up further avenues for profiling plasma or serum to study other ocular diseases. Clinical metadata should be collected whenever blood matrices are studied as age, gender and BMI, blood pressure and smoking status have been found to exert multiple effects on metabolite profiles. In addition, recovery of metabolite information from untargeted studies can be improved with peak annotation tools and DIA workflows.

Dr Eric Chun Yong Chan
National University of Singapore

Read the Original

This page is a summary of: Recent advances in the applications of metabolomics in eye research, Analytica Chimica Acta, February 2018, Elsevier,
DOI: 10.1016/j.aca.2018.01.060.
You can read the full text:

Read

Contributors

The following have contributed to this page