Abstract
Purpose :
To investigate how dexamethasone (Dex) affects the expression of myocilin mRNA, Axin2 mRNA and sFRP1 mRNA, over 10 days of treatment in primary human trabecular meshwork (TM) cells.
Methods :
Primary human trabecular meshwork cells cultured from corneal scleral rims, were treated with 100 nM Dex or DMSO vehicle every day for 10 days. The RNA was isolated each day and quantitative PCR analysis was subsequently carried out for the expression of myocilin mRNA, AXIN2 mRNA and sFRP1 mRNA.
Results :
Myocilin mRNA, AXIN2 mRNA and sFRP1 mRNA were all significantly up regulated in Dex treated cells compared to their vehicle counterparts. The increase of myocilin expression in Dex treated cells started at day 2; AXIN2 expression elevated around day 3, and sFRP1 expression increased around day 7. The highest point of expression of sFRP1 was observed between days 8 and 9 and this correlated with decreased AXIN2 expression.
Conclusions :
: During the course of Dex treatment, there was increased expression of myocilin, AXIN2 and sFRP1 respectively in the TM cells. Myocilin is known to activate Wnt signaling in TM cells; expression of Axin2 is an established biomarker of the Wnt/β-catenin signaling; and sFRP1 is a negative regulator of the Wnt signaling pathway. We therefore propose that in the prolonged presence of Dex, heightened myocilin expression may over activate Wnt and the resultant increase in sFRP1 expression we also observed is suggestive of a regulatory mechanism against this uncontrolled Wnt signaling.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.