Long‐chain unsaturated fatty acids as possible important metabolites for primary angle‐closure glaucoma based on targeted metabolomic analysis

Abstract

Primary angle-closure glaucoma (PACG) is a severe chronic neurodegenerative disease in Asia. Identification of important metabolites associated with PACG is crucial for early intervention and advancing knowledge of the disease mechanism. We applied gas chromatography-mass spectrometry (GC-MS) for targeted metabolomic analysis on serum samples from 38 newly diagnosed PACG patients and 48 controls. Palmitoleic acid (PA), linoleic acid (LA), γ-linolenic acid (GLA) and arachidonic acid (ARA) were identified as important metabolites associated with PACG. PA and GLA were significantly elevated (p < 0.05), while LA and ARA showed a significantly decreased trend (p < 0.05) in PACG group compared with the control group. Also, significant negative correlations were observed between LA and ARA levels and intraocular pressure of the left eye (r = -0.750, p < 0.001; r = -0.729, p < 0.001) and the right eye (r = -0.786, p < 0.001; r = -0.764, p < 0.001). Serum GLA level was positively correlated with intraocular pressure of the left eye (r = 0.233, p = 0.031) and the right eye (r = 0.226, p = 0.036). Our findings revealed a significant difference of the serum free fatty acid metabolic profiles between PACG patients and control subjects. Furthermore, PA, LA, ARA and GLA appear to have clinical applications for the screening of PACG.

A Metabolomics Profiling of Glaucoma Points to Mitochondrial Dysfunction, Senescence, and Polyamines Deficiency

“…The second study compared the metabolome of the serum of individuals with primary angle-closure glaucoma (PACG; n ¼ 38) to that of controls (n ¼ 48), using gas chromatography-mass spectrometry (GC-MS). 12 This study revealed significant differences in the blood of free fatty acids, including palmitoleic, linoleic, c-linoleic, adrenic, and arachidonic acids, the concentration of these metabolites being correlated with the level of ocular pressure.…”

“…This feature is in accordance with the two previous metabolomic studies that indicated a perturbation of the fatty acid metabolism. Burgess et al 11 found only one acyl-carnitine, the long chain palmitoyl-carnitine, with an increased concentration in the POAG signature, whereas Rong et al 12 found five discriminant long-chain free fatty acids; that is, palmitoleic (), linoleic (), c-linoleic (), adrenic (), and arachidonic () acids, but not the acyl-carnitines in their PACG patients.…”

“…Our finding suggested a subtle systemic alteration of carbohydrate metabolism, perceptible in the blood, but that may have escaped detection by the two previous metabolomic studies performed on the blood of POAG 11 and PACG patients. 12 Interestingly, an inverse perturbation of carbohydrate metabolism has been reported in the aqueous humor of a rat model of glaucoma with a decreased concentration of glucose. 13 The POAG signature also is characterized by modified concentrations of six acyl-carnitines.…”

Metabolomic analysis in ophthalmology

“…Moreover, the levels of linoleic and arachidonic acid were negatively associated with intraocular pressure, while serum γ-linolenic acid levels were positively related to intraocular pressure. It might be concluded that long-chain unsaturated fatty acids palmitoleic, linoleic, γ-linolenic, and arachidonic acid are important metabolites associated with PACG and might have potential clinical significance for screening of the disease 66 .…”

Metabolomic Profiles of a Midge (Procladius villosimanus, Kieffer) Are Associated with Sediment Contamination in Urban Wetlands

“…If untargeted molecular features can be identified, they can also help discover specific and novel biomarkers of exposure and toxicity (e.g., [ 27 ]). In contrast, targeted metabolomic approaches (e.g., LC-MS profiling of amine-containing metabolites GC-MS profiling of free fatty acids) report on the abundance of groups of metabolites involved in specific cell responses [ 4 , 28 ]. These targeted techniques provide accurate detail on specific classes of metabolites but are limited as effects on unidentified or unanticipated biochemical pathways are not measured.…”