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Editors Selection IGR 13-1

Basic science: The aqueous humor lipidome in POAG

Comment by Sanjoy Bhattacharya on:

71534 Changes in the Lipidomic Profile of Aqueous Humor in Open-Angle Glaucoma, Cabrerizo J; Urcola JA; Vecino E, Journal of Glaucoma, 2017; 26: 349-355

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Cabrerizo et al. conducted a comparative profiling study of the aqueous humor lipidome from open-angle glaucoma (OAG) patients and control subjects (n = 10 samples per group). Their findings are in agreement with previously published reports on phospholipid, sphingolipid and cholesterol metabolite changes both in human glaucoma and a hypertensive mouse (DBA/2J) model. Particularly, they found several sphingomyelin and cholesteryl ester species to be upregulated in glaucomatous aqueous humor. Authors speculate that observed patterns of lipid metabolism may reflect increased synthesis of sphingomyelins by sphingomyelin synthase or conversely - due to decreased sphingomyelinase activity. They also point out that the increase in sphingomyelin, cholesterol and phosphocholine levels may be implicated in oxidative stress metabolic response in glaucoma.

The work of Cabrerizo et al. adds up to a complex picture of lipid dysregulation arising in glaucoma as well as providing another data resource for new scientific ideas to emerge. The next challenges lie in understanding biological significance of metabolic alterations associated with glaucoma and possibly translating this knowledge into clinical application.

There are some potential limitations to the study. They utilized ultrahigh performance liquid chromatography with time of flight (TOF) mass spectrometry. Different types of mass spectrometry combined with derivatization and prior separation by asymmetric field ion mobility produces superior and higher confidence results than a singular mass spectrometric method alone. An example is the same sample being analyzed by both triple quadrupole and Orbitrap high-resolution mass spectrometers. TOF mass spectrometers necessitate frequent calibration due to inherent drift in the tube. However, while NMR methods are now reliable for targeted metabolomics, they do not handle mixtures of lipids such as the one offered by aqueous humor samples well. As well, the bioinformatic softwares and databases for lipidome analyses have advanced, but still some challenges remain. Despite the limitations, the metabolomics and lipidomic studies are coming along. The details from these studies will eventually complement the proteomic and genomic information and help provide a further detailed picture of the metabolic changes in glaucoma.

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