Abstract
Purpose :
Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease (DED). Research over the past decade has pointed to hyperkeratinization, or the build-up and shedding of keratin protein in the Meibomian gland ducts and at the gland orifice, as the root cause of obstructive MGD. Selenium disulfide (SeS2), a potent keratolytic agent used in dermatologic shampoos for severe dandruff and seborrheic dermatitis, may be used to target meibomian glands’ hyperkeratinization and thus be useful in restoring their normal function in patients with MGD. The objective if this in-vitro study was to determine mechanism of action by which SeS2 effect keratinization, cellular differentiation, proliferation, and adhesion.
Methods :
The keratolytic effect (breakdown of disulfide bonds) of SeS2 was investigated in an ex vivo study of human skin using concentrations of SeS2; 0.1, 1, or 10 mM. The study measured free thiol levels, which are indicative of a decrease in the number of the disulfide bonds that determine the strength of keratin filaments. The keratostatic effect measured by cell turnover was evaluated using a keratinocyte cell line and human skin. Keratinocytes in an in vitro model were incubated with SeS2 (500 µM, 1 mM, and 5 mM). Cell turnover was measured using the FACS propidium iodide (PI) and BrdU incorporation assay.
Results :
SeS2 was shown to cause significant keratolytic activity in human skin with a 60% increase in free thiols relative to control at 10 mM (p < 0.05). In vitro keratinocyte proliferation 28 hours following first exposure was reduced by up to 90%, (p<0.05) at all concentrations. Similarly, the ex vivo studies, measuring BrdU incorporation at 100 uM, 1 mM, and 10 mM showed that the compound significantly reduced cell turnover by up to 35%, (p<0.05), with accumulation of cells in S phase and G2/M phase during cell cycle (decreased cell division).
Conclusions :
The pathogenesis of MGD is a result of accumulation of excess keratin in the gland’s canal and within the lipid. The results suggest that Selenium disulfide works in multiple pathways that are involved in MGD including reduced cell turnover and activity of keratinocytes and softening of keratin through the reduction of disulfide bonds. Hence both in vitro and ex vivo models indicate that Selenium disulfide is a promising candidate for the treatment of MGD.
This is a 2021 ARVO Annual Meeting abstract.