Comprehensive profiling of Asian and Caucasian meibomian gland secretions reveals similar lipidomic signatures regardless of ethnicity

Butovich, Igor A.; Suzuki, Tomo; Wojtowicz, Jadwiga C.; Bhat, Nita; Yüksel, Seher

doi:10.1038/s41598-020-71259-5

Cited by 15 publications

(4 citation statements)

References 60 publications

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“…Of all seven known Elovls, the genes that did not undergo any measurable changes were Elovl2 and Elovl5, with Elovl6 experiencing only an incremental increase from P0 to P7. Considering that ELOVL2 and ELOVL5 act specifically toward polyunsaturated FAs (PUFAs), while ELOVL3 and ELOVL1 control the elongation of saturated and monounsaturated FAs [31,32], the transcriptomic data are consistent with the results of lipidomic experiments, which demonstrated that PUFAs are only minor components of mouse and human meibum [1,2,33], and might not be as relevant to the ocular surface physiology as more saturated FAs.…”

Section: Discussionsupporting

confidence: 72%

Dynamic Changes in the Gene Expression Patterns and Lipid Profiles in the Developing and Maturing Meibomian Glands

Butovich

Wilkerson

2022

IJMS

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Meibomian glands (MGs) and their holocrine secretion—meibum—play crucial roles in the physiology of the eye, providing protection from environmental factors and desiccation, among other functions. Importantly, aging was implicated in the deterioration of the morphology and functions of MGs, and the quantity and quality of meibum they produce, leading to a loss of its protective properties, while the meibum of young individuals and experimental animals provide ample protection to the eye. Currently, the molecular mechanisms of meibum biosynthesis (termed meibogenesis) are not fully understood. To characterize the physiological changes in developing and maturing MGs, we studied the lipidomes and transcriptomes of mouse MGs ranging from newborns to adults. The results revealed a gradual increase in the critical genes of meibogenesis (such as Elovl3, Elovl4, Awat2, and Soat1, among others) that positively correlated with the biosynthesis of their respective lipid products. The MG transcriptomes of young and adult mice were also analyzed using single-cell RNA sequencing. These experiments revealed the existence of multiple unique populations of MG cells (meibocytes, epithelial cells, and others) with specific combinations of genes that encode meibogenesis-related proteins, and identified clusters and subclusters of cells that were tentatively classified as meibocytes at different stages of differentiation/maturation, or their progenitor cells. A hypothesis was formulated that these cells may produce different types of lipids, and contribute differentially to the Meibomian lipidome.

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Section: Discussionsupporting

confidence: 72%

Dynamic Changes in the Gene Expression Patterns and Lipid Profiles in the Developing and Maturing Meibomian Glands

Butovich

Wilkerson

2022

IJMS

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“…Finally, TAG were detected as (M + H) + and (M − FA + H) + ions, as described in our recent publications [21,33].…”

Section: Analytical Instrumentation and Proceduresmentioning

confidence: 99%

Depletion of Cholesteryl Esters Causes Meibomian Gland Dysfunction-Like Symptoms in a Soat1-Null Mouse Model

Butovich

Wilkerson

Yüksel

2021

IJMS

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Previous studies on ablation of several key genes of meibogenesis related to fatty acid elongation, omega oxidation, and esterification into wax esters have demonstrated that inactivation of any of them led to predicted changes in the meibum lipid profiles and caused severe abnormalities in the ocular surface and Meibomian gland (MG) physiology and morphology. In this study, we evaluated the effects of Soat1 ablation that were expected to cause depletion of the second largest class of Meibomian lipids (ML)—cholesteryl esters (CE)—in a mouse model. ML of the Soat1-null mice were examined using liquid chromatography high-resolution mass spectrometry and compared with those of Soat1+/− and wild-type mice. Complete suppression of CE biosynthesis and simultaneous accumulation of free cholesterol (Chl) were observed in Soat1-null mice, while Soat1+/− mutants had normal Chl and CE profiles. The total arrest of the CE biosynthesis in response to Soat1 ablation transformed Chl into the dominant lipid in meibum accounting for at least 30% of all ML. The Soat1-null mice had clear manifestations of dry eye and MG dysfunction. Enrichment of meibum with Chl and depletion of CE caused plugging of MG orifices, increased meibum rigidity and melting temperature, and led to a massive accumulation of lipid deposits around the eyes of Soat1-null mice. These findings illustrate the role of Soat1/SOAT1 in the lipid homeostasis and pathophysiology of MG.

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“…Problems associated with one of the spectrometric studies 61 have been addressed. 63 The advantages of spectroscopic studies over spectrometry have also been addressed, as well as general issues related to spectrometric studies. 10 , 33 It would be interesting to design a study using the same samples where different techniques were the only variable.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Human Meibum Lipid Composition and the Severity of Meibomian Gland Dysfunction: A Spectroscopic Analysis

Nagar,

Ajouz,

Nichols

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose Information on the relationship between meibum lipid composition and severity of meibomian gland dysfunction (MGD) is limited. The purpose of this study was to analyze the molecular components of meibum collected from individuals with no MGD, mild-to-moderate MGD, and severe MGD. Methods Adults with and without MGD were enrolled in a prospective, multicenter, exploratory clinical trial (ClinicalTrials.gov Identifier: NCT01979887). Molar ratios of cholesteryl ester to wax ester (R CE/WE ) and aldehyde to wax ester (R ald/WE ) in meibum samples were measured with 1 H-NMR spectroscopy. Results were evaluated for participants grouped by MGD disease status and severity (non-MGD, mild-to-moderate MGD, and severe MGD), as defined by maximum meibum quality scores, Schirmer test results, and Subject Ocular Symptom Questionnaire responses. Results Sixty-nine meibum samples from 69 individuals were included in the analysis: 24 non-MGD, 24 mild-to-moderate MGD, and 21 severe MGD. Mean R CE/WE was 0.29 in non-MGD, 0.14 in mild-to-moderate MGD ( P = 0.038 vs. non-MGD, 51% lower), and 0.07 in severe MGD ( P = 0.16 vs. mild-to-moderate MGD, 52% lower; P = 0.002 vs. non-MGD, 76% lower). Mean R ald/WE was 0.00022 in non-MGD, 0.00083 in mild-to-moderate MGD ( P = 0.07 vs. non-MGD, 277% higher), and 0.0024 in severe MGD ( P = 0.003 vs. mild-to-moderate MGD, 190% higher; P < 0.001 vs. non-MGD, 992% higher). Conclusions R CE/WE was lowest and R ald/WE was highest in the severe MGD cohort, suggesting that these meibum constituent molar ratios may result from the pathophysiology associated with MGD and can impact ocular surface lipid and tear film homeostasis. These findings may potentially help identify targets for MGD treatment.

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Comprehensive profiling of Asian and Caucasian meibomian gland secretions reveals similar lipidomic signatures regardless of ethnicity

Cited by 15 publications

References 60 publications

Dynamic Changes in the Gene Expression Patterns and Lipid Profiles in the Developing and Maturing Meibomian Glands

Dynamic Changes in the Gene Expression Patterns and Lipid Profiles in the Developing and Maturing Meibomian Glands

Depletion of Cholesteryl Esters Causes Meibomian Gland Dysfunction-Like Symptoms in a Soat1-Null Mouse Model

Relationship Between Human Meibum Lipid Composition and the Severity of Meibomian Gland Dysfunction: A Spectroscopic Analysis

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