Differences in meibomian fatty acid composition in patients with meibomian gland dysfunction and aqueous-deficient dry eye

Joffre, Corinne; Souchier, M.; Grégoire, Stéphane; Viau, Sabrina; Brétillon, Lionel; Acar, Niyazi; Bron, Alain M.; Creuzot‐Garcher, Catherine

doi:10.1136/bjo.2007.126144

Cited by 110 publications

(104 citation statements)

References 28 publications

(24 reference statements)

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“…These results confi rmed independent observations from a number of research laboratories on the presence of large amounts of CEs and WEs in human meibum (18)(19)(20)(21)(22)(23). However, we could not concur on the reported fi ndings on oleamide ( 24 ), Cer, and other typical polar lipids ( 25,26 ).…”

Section: Discussionsupporting

confidence: 71%

Human tear film and meibum. Very long chain wax esters and (O-acyl)-omega-hydroxy fatty acids of meibum

Butovich

Wojtowicz

Molai

2009

Journal of Lipid Research

158

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by various laboratories during the last few decades ( 1-8 ).In TF, meibum is believed to form its outermost layer, which retards evaporation of water from the bulk of TF and from the ocular surface beneath it ( 7 ). Yet another function of meibum is to form a hydrophobic barrier along the margins of the eyelids to contain TF at, and prevent it from leaking out of, the designated ocular surface area ( 2 ). These protective functions imply a very hydrophobic nature of meibum. Indeed, the major meibum components were identifi ed as various wax esters (WEs) and cholesteryl esters (CEs) with long-chain and very longchain FA ( 9-11 ). The information on acylglycerol content of meibum is more limited as no defi nite structural information on the putative meibomian acylglycerols is currently available ( 12, 13 ). Interestingly, lipidomic analyses of human meibum demonstrated that its composition is distinctively different from that of sebum. For example, free cholesterol, squalene, ceramides (Cers), and typical phospholipids were shown to be minor components of meibum ( 9-11, 14, 15 ), although they dominated in the skin ( 16,17 ).Meibum has been analyzed using various experimental techniques, discussion of which goes beyond the scope of this article. Recently, we published preliminary results on the lipid composition of human meibum and tears ( 9-11, 15 ). The major method employed in these studies was normal phase high performance liquid chromatography in combination with atmospheric pressure chemical ionization mass spectrometry (NP HPLC-MS). The main advantage of the NP HPLC is its ability to separate different classes of lipids. For example, mono-, di-, and triacylglycerols (MAGs, DAGs, and TAGs, respectively) elute as three distinctively different groups of HPLC peaks and so do other groups of lipids (free FAs and their amides and Meibum is a lipid-rich secretion that is produced by Meibomian glands located at the ocular lid margins of both upper and lower eyelids of various mammals and humans. Meibum is an intrinsic part of the human tear fi lm (TF), the main role of which is to protect the ocular surface from dehydration. Among other proposed functions of TF are antimicrobial, lubricatory, and nutritional ones. For general information on meibum and TF, the reader is advised to read earlier comprehensive reviews published

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Section: Discussionsupporting

confidence: 71%

Human tear film and meibum. Very long chain wax esters and (O-acyl)-omega-hydroxy fatty acids of meibum

Butovich

Wojtowicz

Molai

2009

Journal of Lipid Research

158

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“…Therefore, they could not be a major source of the LCFA and VLCFA either. Our current findings show that such a source is Chl-E. Interestingly, our data show that the longest fatty acid detected in Chl-E of human meibum has up to 34 carbons, far longer than 26 carbons reported by Joffre et al (29,30) and, possibly, even longer than that if the Chlcontaining HPLC peaks 19 and 20 are indeed Chl-E. Also, a large portion of the LCFA and VLCFA were monounsaturated. This discrepancy has most likely to do with the well-known fact that long chain fatty acids are unstable under the conditions of GC-MS analysis and quickly decompose at high temperatures at which the GC columns typically operate.…”

Section: Discussionsupporting

confidence: 58%

“…The VLCFA also suffer from low volatility, which is inversely proportional to their length and molecular mass. Therefore, the notable absence of VLCFA beyond C 26 for saturated compounds, and anything beyond C 18:1 for unsaturated VLCFA in the data by Joffre et al (29,30) can be related to these limitations of the GC-MS technique. The exact location and geometry of the double bonds in the structures of monounsaturated Chl-E from meibum remain to be investigated.…”

Section: Discussionmentioning

confidence: 94%

“…Interestingly, at least half of the Chl-containing compounds detected in human meibum eluted later than the longest Chl-E standards, C 22 (29,30) were esterified into. In their study, the source of C 20 to C 26 fatty acids in human meibum remained unknown as the entire meibum samples were transmethylated immediately after collection in a reaction with methanolic boron trifluoride and then analyzed by GC-MS.…”

Section: Discussionmentioning

confidence: 98%

“…Typically, the analyses were performed using GLC or GC-MS after transesterification of the entire lipid pool (7,29,30), which precluded researchers from identifying the intact lipid species present in meibum. As 1) WE and Chl-E were estimated to comprise more than two-thirds of the entire lipid pool of human meibum (7), and 2) WE detected in our experiments (25,26) were mostly C 18 -based, there was a distinctive possibility that it is the Chl-E that have VLCFA in their structures.…”

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confidence: 99%

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Cholesteryl esters as a depot for very long chain fatty acids in human meibum

Butovich

2009

Journal of Lipid Research

109

151

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Human meibomian gland secretions (also known as meibum) were analyzed for the presence of cholesteryl esters (Chl-E) using HPLC in combination with atmospheric pressure chemical ionization mass spectrometry. A special procedure based on detection of the in-source generated ion m/z 369 was developed to monitor all Chl-E simultaneously. The structures of the detected compounds were studied using in-source and postsource fragmentation of the precursor (M1H) 1 ions. In concordance with previous studies, Chl-E were found in all of the tested samples and comprised ?31% of the entire lipid pool (w/w, dry weight). There were at least 20 different saturated and unsaturated Chl-E species observed, whose fatty acid residues ranged from C18 to C34. Monounsaturated fatty acids were the most visible components of the Chl-E pool. The eleven most prominent compounds were: C20:0-, C22:1-, C22:0-, C24:1-, C24:0, C25:0-, C26:1-, C26:0-, C28:1-, C28:0-, and C30:1-Chl-E. Other Chl-containing compounds were detected but not identified at the time. Therefore, Chl-E are a depot for very long chain saturated and monounsaturated fatty acids in human meibum. Meibomian glands that are located at the margins of human upper and lower eyelids produce secretions (also known as meibum) formed of a complex mixture of various nonpolar and polar lipids (1-31). The primary role of meibum is to form the bulk of a so-called preocular tear film lipid layer (TFLL), which covers the entire ocular surface and fulfills various roles including antievaporatory, antibacterial, lubricating, nutritional, and others. The lipid composition of TFLL is critical for maintaining the stability of the preocular tear film, deterioration of which has been associated with various ocular diseases and pathological conditions. Human meibum has been shown to have a large number of diverse lipid species, including wax esters (WE) (3, 5-7, 12, 16-20, 25, 26), cholesteryl esters (Chl-E) (3,5,7,11,12,18,20,25,26), mono-, di-, and triacyl glycerols (3, 5-7, 14, 16-18, 20, 21, 25, 26), hydrocarbons (6), free fatty acids (31), sterols (1, 3-7, 9, 11-13, 16-20), phospholipids (2,6,7,15,19,21,22,25,26), ceramides (6, 21), and many other poorly identified lipid compounds. Historically, the main methods used to characterize meibomian lipids were TLC (3-5, 15, 20-22), gas-liquid chromatography (6-10, 13), and gas chromatography-electron ionization GC-MS (11, 15, 20-22, 30, 31), HPLC with UV detection (15,(20)(21)(22), infrared spectrometry (27, 28), and, more recently, various types of modern mass spectrometry (MS) techniques with or without HPLC (16,17,19,23,25,26). Recently, we developed and implemented normal phase (NP) HPLC-MS protocols that allowed us to evaluate the lipid composition of human meibum (25,26). This approach has proven to be well-suited for analyses of very hydrophobic components of human meibum, which in our hands was found to be consisted primarily of WE, Chl-E, and triacyl glycerols, with all other compounds being minor constituents. For example, the over...

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Identification of genes mediating branched chain fatty acid elongation

Wang

Park

et al. 2019

FEBS Letters

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Saturated branched chain fatty acids (BCFA) terminating with either a prop‐2‐yl (iso) or sec‐butan‐2‐yl (anteiso) group are common bioactive food components consumed from beef, fish, and dairy products. Little is known about the endogenous metabolism of BCFA and the enzymes mediating their interconversions. By using transient transfection studies, we report for the first time the substrate specificity of the elongase of very long chain fatty acids (ELOVL)1‐7 toward anteiso‐15:0 and iso‐18:0, and assessed competition between BCFA and normal saturated fatty acids (n‐SFA). ELOVL6 mediates elongation of anteiso‐15:0→anteiso‐17:0, while ELOVL3 is active toward iso‐18:0→iso‐20:0. Competition studies reveal n‐16:0 competes with anteiso‐15:0 for ELOVL6, while n‐18:0 competes with iso‐18:0 for ELOVL3. These competitions for elongation may have implications in specialized tissues where both BCFA and n‐SFA are present at comparable levels.

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Differences in meibomian fatty acid composition in patients with meibomian gland dysfunction and aqueous-deficient dry eye

Cited by 110 publications

References 28 publications

Human tear film and meibum. Very long chain wax esters and (O-acyl)-omega-hydroxy fatty acids of meibum

Human tear film and meibum. Very long chain wax esters and (O-acyl)-omega-hydroxy fatty acids of meibum

Cholesteryl esters as a depot for very long chain fatty acids in human meibum

Identification of genes mediating branched chain fatty acid elongation

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