June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
The effects of inhibition of PDGFR-β in retinal endothelial cells within the retinoblastoma tumor microenvironment
Author Affiliations & Notes
  • Zachary K. Goldsmith
    Ophthalmology, University of Tennessee Health Science Center, Germantown, Tennessee, United States
  • William Coppess
    Ophthalmology, University of Tennessee Health Science Center, Germantown, Tennessee, United States
  • Kelley Yuan
    Ophthalmology, University of Tennessee Health Science Center, Germantown, Tennessee, United States
  • Andrew S Irvine
    Ophthalmology, University of Tennessee Health Science Center, Germantown, Tennessee, United States
  • Rachel Brennan
    Ophthalmology, University of Tennessee Health Science Center, Germantown, Tennessee, United States
    Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States
  • Matthew W Wilson
    Ophthalmology, University of Tennessee Health Science Center, Germantown, Tennessee, United States
    Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee, United States
  • Vanessa Marie Morales
    Ophthalmology, University of Tennessee Health Science Center, Germantown, Tennessee, United States
    Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Footnotes
    Commercial Relationships   Zachary Goldsmith, None; William Coppess, None; Kelley Yuan, None; Andrew Irvine, None; Rachel Brennan, None; Matthew Wilson, None; Vanessa Morales, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1781. doi:
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    • Get Citation

      Zachary K. Goldsmith, William Coppess, Kelley Yuan, Andrew S Irvine, Rachel Brennan, Matthew W Wilson, Vanessa Marie Morales; The effects of inhibition of PDGFR-β in retinal endothelial cells within the retinoblastoma tumor microenvironment. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1781.

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

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Abstract

Purpose : Retinoblastoma (Rb) is a highly angiogenic tumor, for which anti-VEGF therapies have shown limited success in clinical setting. This illustrates the need for more novel therapeutics. Previous work from our lab showed inhibition of PDGFR-β inhibited Rb cell proliferation in vitro. However, novel therapies must not only target tumor cells but also how they affect the tumor microenvironment.

Methods : We investigated the role of the PDGFR-β in the tumor microenvironment and how inhibition of this signaling pathway impacts angiogenesis in human retinal microvascular endothelial cells (hRECs). Rb monocultures and co-cultures with hRECs were evaluated for the production of the angiogenic proteins PDGF and VEGF after treatment with imatinib mesylate, a small molecule kinase inhibitor. We performed tube formation assay in hRECs to investigate if PDGF played a role in structural integrity of the vasculature.

Results : We found that inhibition of the PDGFR-β signaling pathway through imatinib mesylate affects both paracrine and autocrine angiogenic mechanisms in Rb cells. Production of VEGF is also affected by inhibition of this signaling pathway.

Conclusions : More studies are underway to elucidate if the use of imatinib mesylate will also regulate hRECs cell survival. This is of critical importance as success of treatment also depends on the ability of the normal tissues to remain healthy after sensitization and/or killing of the Rb tumor.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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