Changes in meibomian fatty acids and clinical signs in patients with meibomian gland dysfunction after minocycline treatment

Souchier, M.; Joffre, Corinne; Grégoire, Stéphane; Brétillon, Lionel; Muselier, A.; Acar, N.; Beynat, J.; Bron, Alain M.; d’Athis, Philippe; Creuzot‐Garcher, Catherine

doi:10.1136/bjo.2007.133900

Cited by 71 publications

(63 citation statements)

References 21 publications

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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: Discussionmentioning

confidence: 49%

“…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: 96%

“…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: 99%

“…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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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

mentioning

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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“…[25][26][27][28] It has been well documented that meibomian glands dysfunctions are associated with ocular irritation and ocular surface staining. 20,[29][30][31] Our multi-regression analysis showed that the staining score of the inferior conjunctiva and cornea were correlated with the meibomian glands dysfunction scores. These results were not too surprising because these regions are frequently in contact with the lid margins during blinking.…”

Section: Discussionmentioning

confidence: 97%