Purchase this article with an account.
Wei-Sheng Chen, Zhiyi Cao, Noorjahan A Panjwani; Verteporfin Inhibits YAP Activation in Trabecular Meshwork Cells without Light Stimulation: Implication for Glaucoma Treatment. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3284. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Glaucoma affects over 60 million adults worldwide. Verteporfin, a photosensitizer, is used in photodynamic therapy to treat age-related macular degeneration. Published studies have shown that Verteporfin inhibits YAP activation without light stimulation. YAP is a mechanotransducor, and YAP activation in the nucleus through interaction with TEAD has emerged as an important pathway in the pathogenesis of glaucoma. We hypothesize that targeting YAP by Verteporfin may ameliorate glaucoma.
To assess the effect of Verteporfin on trabecular meshwork (TM) cell-mediated collagen gel contraction, TM cells were embedded in collagen gel in the presence or absence of Verteporfin for 48 hr. Areas of collagen gel sizes were quantified by ImageJ. To determine the effect of Verteporfin on fibronectin-mediated cell spreading, TM cells were pretreated with Verteporfin, detached, and plated on fibronectin-coated wells for 2 hours. Actin filaments were stained with Acti-Stain 555-labeled phalloidin and cell spreading areas were quantified by ImageJ. Gene expression of connective tissue growth factor (CTGF) in TM cells was analyzed by qPCR. Cytotoxic effect of Verteporfin was assessed by WST-1.
We demonstrated here that Verteporfin (i) abolishes TM cell-mediated collagen gel contraction in a dose-dependent manner, (ii) has no significant toxicity below 2 μM, (iii) reduces fibronectin-mediated TM cell adhesion and spreading, (iv) interferes with fibronectin-mediated stress fiber reorganization, and (v) attenuates TGF-β2-induced upregulation of CTGF.
Our results indicate that Verteporfin without light stimulation may reduce intraocular pressure by facilitating aqueous humor outﬂow through the TM-Schlemm’s canal system.
This PDF is available to Subscribers Only