Abstract
Purpose :
Meibomian gland dysfunction is believed to be the leading cause of Dry Eye Disease (DED). While the higher prevalence of DED in women has implied the possibility of sex-related differences in the composition of meibum, the role of sex in the biosynthesis of meibum (meibogenesis) remains unclear. The purpose of this study was to determine if there were any major sex-specific differences in the expression patterns of genes related to meibogenesis, and in the lipid composition of meibum.
Methods :
Tarsal plates (TP) of deceased donors and surgical samples from live donors undergoing lid surgery were collected. Only the samples with RNA integrity numbers between 7 and 10 were used for the analyses. Sections of TP were analyzed using HTA-2_0 mRNA microarrays (from Affymetrix), and the data was analyzed using Expression and Transcriptome Analysis Consoles (from Affymetrix) and SigmaStat (from Systat Software, Inc.). The default filter criteria – 1) fold change (linear) < -2 or fold change (linear) > 2, and 2) ANOVA p-value (condition pair) < 0.05, were used to analyze the data. Samples of meibum were collected and analyzed using established chromatographic and mass-spectrometric procedures.
Results :
The gene level differential expression analyses of almost 44699 protein-coding transcripts revealed that only 656 genes were differentially expressed, none of which were deemed to be related to the metabolism and storage of lipids in general, and biosynthesis of meibum, specifically. Importantly, the expression levels of ELOVL1-7, SCD, FAR1 & 2, DHCR24, SOAT1 & 2, AWAT1 & 2, HMGCS1 & 2, HMGCR, ACAT1 &2, DGAT, FASN, FADS, and PLIN1-5, among others, were high, and demonstrated no statistically significant differences between males and females. No major differences were observed in their lipid profiles, either, with the major detected intact lipids deviating from the mean values by ≤15%, on average. The expression levels of major house-keeping and reference genes were also statistically indistinguishable. However, known sex-specific transcripts, such as XIST, DDX3Y, UTY, EIF1AY, and KDM5D, clearly produced sex-specific expression patterns.
Conclusions :
Our analyses demonstrated no major differences between the two sexes, indicating that the biosynthetic pathways in meibogenesis are similar in both males and females, and produce a secretion with a highly conserved composition.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.