July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The effect of Dex on MYOC, AXIN2 and sFRP1 expression in primary human TM cells
Author Affiliations & Notes
  • Jie J Zheng
    Department of Ophthalmology, Stein Eye Institute, UCLA, Los Angeles, California, United States
  • Chi Zhang
    Department of Ophthalmology, Stein Eye Institute, UCLA, Los Angeles, California, United States
  • Elizabeth Tannous
    Department of Ophthalmology, Stein Eye Institute, UCLA, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Jie Zheng, None; Chi Zhang, None; Elizabeth Tannous, None
  • Footnotes
    Support  NIH Grant GM100909 and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1658. doi:
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      Jie J Zheng, Chi Zhang, Elizabeth Tannous; The effect of Dex on MYOC, AXIN2 and sFRP1 expression in primary human TM cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1658.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Recently, we found that a broad-spectrum small-molecule Wnt inhibitor that targets the Wnt receptor Frizzled abrogates some dexamethasone (Dex)-induced phenotypes of the TM cells suggesting that abnormal Wnt signaling may exhibit pleiotropic roles in glaucomatous TM. The result was somewhat unexpected because the expression of sFRP1, a Wnt signaling antagonist, is up-regulated in the glaucomatous TM cells. To reconcile those data, we examined how Dex affected the expression of MYOC, AXIN2, a marker of Wnt signaling activation, and sFRP1, over 10 days of Dex-treatment in primary human TM cells.

Methods : Primary human TM 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 MYOC, AXIN2, and sFRP1.

Results : Expression of MYOC, AXIN2, and sFRP1 were all significantly up-regulated in Dex-treated cells compared to their vehicle counterparts. The MYOC expression peaked around day 6 or 7 while highest point of expression of sFRP1 was observed between days 8 and 9 and this correlated with decreased AXIN2 expression.

The myocilin protein levels also increased in a time-dependent manner during Dex-treatment. However, they trailed behind the increase of the MYOC mRNA levels. Nevertheless, it seemed that the myocilin protein levels were synchronized with the mRNA expressions of AXIN2 and sFRP1. When the expressions of AXIN2 and sFRP1 reached to the highest levels, MYOC expressions declined.

Conclusions : Our data showed that an increased expression of MYOC, AXIN2, and sFRP1 was observed in HTM cells in a time-depended manner after treatment with Dex. Moreover, the sequence of the expression was first led by MYOC, followed by AXIN2 and last was sFRP1. Based on the result, we propose that Dex-induced Wnt signaling activation may be a “protective” mechanism of the TM cells. Nevertheless, to keep the homeostatic state of the TM tissue, the activated Wnt signaling has to be “reset” after an external insult such as steroid treatment. Therefore, prolonged steroid-treatment could persistently activate Wnt signaling that then leads to abnormal Wnt signaling activation and eventually causes glaucomatous phenotypes. Plausibly, sFRP1 could be the negative feedback mechanism generated by “stressed” TM cells to suppress the abnormal Wnt signaling activities.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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