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Verteporfin without light stimulation inhibits YAP activation in trabecular meshwork cells: Implications for glaucoma treatment.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2015 Oct 16; Vol. 466 (2), pp. 221-5. Date of Electronic Publication: 2015 Sep 08. - Publication Year :
- 2015
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Abstract
- Verteporfin, a photosensitizer, is used in photodynamic therapy to treat age-related macular degeneration. In a glaucoma mouse model, Verteporfin without light stimulation has been shown to reduce intraocular pressure (IOP) but the mechanism is unknown. Recent studies have shown that Verteporfin inhibits YAP without light stimulation in cancer cells. Additionally, YAP has emerged as an important molecule in the pathogenesis of glaucoma. We hypothesize that YAP inactivation by Verteporfin in trabecular meshwork (TM) may be related to the reduced IOP observed in vivo. As contractility of TM tissues is associated with IOP, collagen gel contraction assay was used to assess the effect of Verteporfin on contractility of TM cells. Human TM cells were embedded in collagen gel and treated with Verteporfin for 48 h. Areas of collagen gel sizes were quantified by ImageJ. To assess the effect of Verteporfin on the expression of YAP, human TM cells were treated with Verteporfin for 24 h and the expression of YAP was determined by Western blotting. To determine the cytotoxic effect of Verteporfin, human TM cells were treated with Verteporfin for 24 h, and then the cell viability was assessed by WST-1. We demonstrated here that Verteporfin (i) abolishes TM cell-mediated collagen gel contraction in a dose-dependent manner, (ii) attenuates expression of YAP and CTGF (connective tissue growth factor, a direct YAP target gene) in a dose-dependent manner, and (iii) has no significant cytotoxicity below 2 μM. Taken together, Verteporfin may facilitate aqueous humor outflow through the conventional outflow system and reduce IOP by inactivating YAP.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Cycle Proteins
Cells, Cultured
Collagen metabolism
Glaucoma physiopathology
Humans
Intraocular Pressure drug effects
Light
Nuclear Proteins metabolism
Photosensitizing Agents therapeutic use
Porphyrins therapeutic use
Transcription Factors metabolism
Verteporfin
Glaucoma drug therapy
Nuclear Proteins antagonists & inhibitors
Photosensitizing Agents pharmacology
Porphyrins pharmacology
Transcription Factors antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 466
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 26361148
- Full Text :
- https://doi.org/10.1016/j.bbrc.2015.09.012