September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Verteporfin inhibits growth of human ocular glioma in vitro without light activation
Author Affiliations & Notes
  • Ahmad Al Moujahed
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Katarzyna Brodowska
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Tomasz Stryjewski
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Joanna Cichy
    Dept. of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
  • Evangelos S Gragoudas
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Demetrios G. Vavvas
    Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Ahmad Al Moujahed, None; Katarzyna Brodowska, None; Tomasz Stryjewski, None; Joanna Cichy, None; Evangelos Gragoudas, QLT Phototherapeutics, Inc. (R); Demetrios Vavvas, None
  • Footnotes
    Support  National Eye Institute grant EY014104 - MEEI Core Grant
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4109. doi:
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      Ahmad Al Moujahed, Katarzyna Brodowska, Tomasz Stryjewski, Joanna Cichy, Evangelos S Gragoudas, Demetrios G. Vavvas; Verteporfin inhibits growth of human ocular glioma in vitro without light activation. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4109.

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

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Abstract

Purpose : Optic nerve gliomas (ONGs) comprise 2-5% of all pediatric central nervous system (CNS) tumors and are the most common CNS tumors in patients with neurofibromatosis type 1 (NF1). Treatment options are limited and are often associated with significant morbidity. Verteporfin (VP), a benzoporphyrin derivative, is clinically used as a photosensitizer in photodynamic therapy for neovascular macular degeneration and ocular tumors. Recent studies indicate that VP inhibits the growth of retinoblastoma and other tumor cells without photoactivation through inhibition of YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma LN229 and SNB19 cell growth in vitro.

Methods : Human glioma cell lines LN229 and SNB19 were treated with VP. Cell growth was assessed by trypan blue exclusion test and MTT assay. Western blot analyses were performed to check the expression of YAP-TEAD downstream signaling molecules and other pathways such as mTOR and Akt.

Results : Verteporfin treatment without light activation inhibited LN229 and SNB19 cell growth, increased their doubling time, and reduced cell viability in a dose-dependent manner. Treatment of glioma cells with VP was associated with downregulation of YAP-TEAD-associated downstream signaling molecules including c-myc, axl, CTGF, cyr61, and survivin. In addition, VEGFA and pluripotency marker Oct4 were downregulated. Moreover, VP treatment activated autophagy and p38 MAPK pathway. However, it did not affect mTOR and Akt pathway.

Conclusions : VP without light activation is a potent inhibitor of cell growth in glioma LN229 and SNB19 cells and may provide a novel adjuvant therapeutic tool in treating ocular glioma patients.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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