Metabolomic & Proteomic Approaches to Eye Disease

Article: A View to Improving AMD and Vision Loss
Source: Technology Networks
Published: March 30, 2021

This article provides a commentary on recent scientific approaches in metabolomics and proteomics and how they shed light on the causes of eye diseases such as age-related macular degeneration (AMD) and dry eye disease (DED). For instance, researchers in Finland and Singapore are investigating the mechanisms involved in AMD through advanced liquid chromatography mass spectrometry (LC-MS) with SWATH Acquisition (a more comprehensive method for detecting all the metabolites present in complex samples) to examine the proteomic profiles of tear samples. Their data showed that protein quantities varied with age, and suggest that in healthy aging, cell growth and survival decrease while immune response and inflammation increase. Another research team in Singapore, with collaborators in the U.S., is using LC-MS to examine the metabolic profiles of serum samples in wet AMD patients. As compared to healthy controls, those with wet AMD had higher levels of glycerophospholipids, amino acids, and omega fatty acids. Comparison of sera between anti-VEGF drug responders and suboptimal responders further found that glycerophospholipids, such as lysophosphatidylcholine, were higher in suboptimal responders, implicating glycerophospholipid metabolism as a contributor to suboptimal response.

Mass spectroscopy is also useful in proteomic studies of dry eye disease. For example, LC-MS based proteomic analysis of tears from DED patients undergoing treatment with either flourometholone (FML) or polyvinyl alcohol (PA) revealed protein biomarkers that could be used to predict which patients would respond best to management with either of these drugs. Dry eye disease also affects many glaucoma patients as a side effect of topical glaucoma medications. In such cases, analysis of tear proteomes could help to identify patients who would most benefit from switching to preservative-free eye drops. A metabolomic/proteomic approach to identify biomarkers of disease is useful to both better understand the underlying mechanisms of diseases and to guide treatment that would benefit the right patients at the right time. The author concludes, "This is precision medicine, and you do not get precision medicine without the sensitive and precise quantification of molecules."

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