Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers

Metabolic phenotyping involves the comprehensive analysis of biological fluids or tissue samples. This analysis allows biochemical classification of a person's physiological or pathological states that relate to disease diagnosis or prognosis at the individual level and to disease risk factors at the population level. These approaches are currently being implemented in hospital environments and in regional phenotyping centres worldwide. The ultimate aim of such work is to generate information on patient biology using techniques such as patient stratification to better inform clinicians on factors that will enhance diagnosis or the choice of therapy. There have been many reports of direct applications of metabolic phenotyping in a clinical setting.

Neural membranes contain several classes of glycerophospholipids which turnover at different rates with respect to their structure and localization in different cells and membranes. The glycerophospholipid composition of neural membranes greatly alters their functional efficacy. The length of glycerophospholipid acyl chain and the degree of saturation are important determinants of many membrane characteristics including the formation of lateral domains that are rich in polyunsaturated fatty acids. Receptor-mediated degradation of glycerophospholipids by phospholipases A(l), A(2), C, and D results in generation of second messengers such as arachidonic acid, eicosanoids, platelet activating factor and diacylglycerol. Thus, neural membrane phospholipids are a reservoir for second messengers. They are also involved in apoptosis, modulation of activities of transporters, and membrane-bound enzymes. Marked alterations in neural membrane glycerophospholipid composition have been reported to occur in neurological disorders. These alterations result in changes in membrane fluidity and permeability. These processes along with the accumulation of lipid peroxides and compromised energy metabolism may be responsible for the neurodegeneration observed in neurological disorders.