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Thao N Yeh, Meng C Lin, Karsten Gronert; Meibum Lipid Mediators in Isotretinoin Exposed vs. Unexposed Individuals. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2766.
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To our knowledge, bioactive lipid mediators in meibum have not been defined. We aimed to determine meibum lipid mediator (1) profile, (2) relationships to ocular signs and symptoms and (3) differences between isotretinoin exposed (ISO) and unexposed (NISO) groups.
Single-visit cohort study with ISO and NISO groups. Clinical tests: tear lipid layer (TLL) thickness (Lipiview), non-invasive tear breakup time (NITBUT), Meibomian gland expression (MGE), and Standardized Patient Evaluation of Eye Dryness (SPEED) II and Visual Analog Score (VAS) questionnaires. Meibum were collected with dacron swabs, lipid mediators were identified and quantified using an AB Sciex QTRAP 4500 LC/MS/MS system. Analysis used chi-square and Mann-Whitney tests and Pearson correlation (Stata/IC 14.0).
NISO [Age(SD)=25.8(11.6) years] and ISO [Age(SD)=22.0(4.8) years] completed 26 and 22 participants, respectively. Polyunsaturated fatty acids and lipid mediators identified included arachidonic acid (AA), docosahexaenoic acid (DHA), 5- and 12-hydroxyeicosatetraenoic acids (5-HETE and 12-HETE), prostaglandins E2 and D2 (PGE2 and PGD2), and thromboxane B2 (TXB2). ISO had significantly (p<0.05) lower levels (pg/sample) of 5-HETE, PGE2, PGD2, and TXB2 but higher levels of DHA compared to NISO. AA levels were similar between groups. ISO also had significantly (p<0.05) lower PGD2/AA, PGE2/AA and TXB2/AA ratios compared to NISO. Symptoms (SPEED and VAS) were significantly worse for ISO (p<0.05). Clinical signs were similar between groups and not associated with lipid mediator levels. Significant differences in PGD2 actual (pg/sample; p<0.001) and relative (p<0.001) levels between NISO (18853±13137 and 5428±4094, respectively) and ISO (5858±8291 and 1692±2156, respectively) detected in meibum were particularly striking.
To our knowledge, this is the first report of PGE2, PGD2 and TXB2, which are primary drug targets for NSAIDS and corticosteroids, in human meibum. Their presence in meibum and lower levels in ISO meibum suggest previously unrecognized roles of prostanoids in MG physiology and/or pathophysiology. Meibum PGD2 is of particular interest as it is an established mediator of allergic immune responses, a major product of mast cells, and associated with elevated sebum levels in pilosebaceous units. Prostanoids function in MG physiology, regulation by isotretinoin, and potential role in MGD warrants further investigation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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