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Jianzhong CHEN, Kelly K Nichols; Chain Length and Saturation Levels of Molecular Species of Neutral Lipids in Dry Eye Patients. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2234. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Molecular alterations in meibum lipids, which are believed to be a predominant reason for evaporative dry eye disease (DED), are largely unknown. To better understand the underlying mechanisms, we compared the neutral lipid profiles of four major classes, including wax esters (WE), cholesteryl esters (CE), ω Type I-St diesters (DE1), and α, ω Type-II diesters (DE2), between DED and normal groups to evaluate differences in these lipids related to chain length and saturation levels as predictors of DED.
This study is an in-depth data analysis of previously collected and analyzed meibum samples. The method for sample preparation and data acquisition were the same as described previously (Chen J, et al. IOVS 2015; 56: ARVO E-Abstract 342). Briefly, lipids of meibum sample solutions from a total of 66 subjects (40 normal, 26 postmenopausal women with DED) were detected on a high-resolution mass spectrometer (maXis 4G UHR-QTOF, Bruker; Billerica, MA) in positive ion mode by direct infusion and electrospray ionization. The resultant peak lists for these samples were statistically analyzed by student’s t test. In contrast to our previous work focusing only on statistically different lipids, all detected species were compared within each class for relative intensity, intensity ratio (DED/N), and corresponding p-value.
The overall ratio of peak intensity (DED vs normal) for each class decreases as the chain length increases, however each class demonstrates a different pattern. For WE, species with shorter (nc < 40), intermediate (nc = 40-43), and longer (nc ≥ 44) chains, the intensity ratio were consistently >1, about 1, and variable, respectively. Specifically, the variability appeared to be associated with unsaturation level; while the ratio for most WE molecular species decreased significantly, some including 45:3, 46:4, 47:3, 49:3, 46:0 and 48:0 were almost the same for DED/N. For CE with longer chains (nc ≥ 24), the ratio was consistently less than 1; however, with the exception of 25:1 and 27:1 which were close to 1 (see figure). Similarly, for DE1 and DE2 with chain length ≥ 48 and ≥64, respectively, the ratio was consistently <1 with few exceptions.
Evaporative dry eye disease is likely related to a dysfunction in synthesis of neutral lipids of very long chain and appropriate unsaturation, and differences are exhibited both within and between major lipid classes.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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