Prostaglandin E2 and F2α Alter Expression of Select Cholesteryl Esters and Triacylglycerols Produced by Human Meibomian Gland Epithelial Cells

Purpose: PGF(2 alpha) analogs are commonly used to treat glaucoma and are associated with higher rates of meibomian gland dysfunction (MGD). The purpose of this study was to evaluate the physiological effects of PGF(2 alpha) and PGE(2) on immortalized human meibomian gland epithelial cells (HMGECs). Methods: HMGECs were immunostained for the 4 PGE(2) receptors (EP1, EP2, EP3, and EP4) and 1 PGF(2 alpha) receptor (FP) and imaged. Rosiglitazone-differentiated HMGECs were exposed to PGF(2 alpha) and PGE(2) (10(-9) to 10(-6) M) for 3 hours. Cell viability was assessed by an adenosine triphosphate-based luminescent assay, and lipid extracts were analyzed for cholesteryl esters (CEs), wax esters (WEs), and triacylglycerols (TAGs) by ESI-MSMSALL in positive ion mode by a Triple TOF 5600 Mass Spectrometer using SCIEX LipidView 1.3. Results: HMGECs expressed 3 PGE(2) receptors (EP1, EP2, and EP4) and the 1 PGF(2 alpha) receptor (FP). Neither PGE(2) nor PGF(2 alpha) showed signs of cytotoxicity at any of the concentrations tested. WEs were not detected from any of the samples, but both CEs and TAGs exhibited a diverse and dynamic profile. PGE(2) suppressed select CEs (CE 22:1, CE 26:0, CE 28:1, and CE 30:1). PGF(2 alpha) dose dependently increased several CEs (CE 20:2, CE 20:1, CE 22:1, and CE 24:0) yet decreased others. Both prostaglandins led to nonspecific TAG remodeling. Conclusions: PGE(2) and PGF(2 alpha) showed minimal effect on HMGEC viability. PGF(2 alpha) influences lipid expression greater than PGE(2) and may do so by interfering with meibocyte differentiation. This work may provide insight into the mechanism of MGD development in patients with glaucoma treated with PGF(2 alpha) analogs.

Automated summary

The study evaluated the physiological effects of PGF(2 alpha) and PGE(2) on immortalized human meibomian gland epithelial cells. The results showed that PGF(2 alpha) had a greater impact on lipid expression and may interfere with meibocyte differentiation. This has important implications for understanding the mechanism of MGD development in patients with glaucoma treated with PGF(2 alpha) analogs.