Small-molecule inhibition of Wnt signaling abrogates dexamethasone-induced phenotype of primary human trabecular meshwork cells

- Dex induced myocilin expression in primary human TM cells is decreased with Wnt signaling inhibition.
- Dex mediated AXIN2 expression is decreased with Wnt signaling inhibition.
- Extracellular matrix protein expression in primary human TM cells treated with Dex is decreased with Wnt signaling inhibition.
- Small molecule Wnt signaling inhibition reduces Dex mediated collagen secretion by primary human TM cells.

Trabecular meshwork (TM) cells are the governing regulators of the TM structure. When the functionality of these cells is impaired, the structure of the TM is perturbed which often results in increased ocular hypertension. High intraocular pressure is the most significant risk factor for steroid-induced glaucoma. Dexamethasone (Dex)-induced phenotype of TM cells is widely utilized as a model system to gain insight into mechanisms underlying damaged TM in glaucoma. In this study, to assess the possible role of abnormal Wnt signaling in steroid-induced glaucoma, we analyzed the effects of small-molecule Wnt signaling modulators on Dex-induced expression extracellular matrix proteins of primary human TM cells. While Dex-treated TM cells exhibited increased collagen and fibronectin expression, we found that Wnt signaling inhibitor 3235-0367 suppressed these Dex-induced effects. We therefore propose that Wnt signaling plays an important role in Dex-mediated impairment of TM cell functions. Moreover, the use of small-molecule Wnt signaling inhibitors to treat TM cells may provide an opportunity of restoring TM tissue in steroid-induced glaucoma.