June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Inhibition of PDGFR-β Decreases Pro-Survival Signaling of Retinoblastoma in vitro
Author Affiliations & Notes
  • Madison Ritter
    Ophthalmology, Hamilton Eye Institute, UTHSC, Memphis, Tennessee, United States
  • William Coppess
    Ophthalmology, Hamilton Eye Institute, UTHSC, Memphis, Tennessee, United States
  • Zachary K. Goldsmith
    Ophthalmology, Hamilton Eye Institute, UTHSC, Memphis, Tennessee, United States
  • Rachel Brennan
    Oncology, St. Jude Childrens Research Hospital, Memphis, Tennessee, United States
    Ophthalmology, Hamilton Eye Institute, UTHSC, Memphis, Tennessee, United States
  • Matthew W Wilson
    Ophthalmology, Hamilton Eye Institute, UTHSC, Memphis, Tennessee, United States
    Surgery, St. Jude Childrens Research Hospital, Memphis, Tennessee, United States
  • Vanessa Marie Morales
    Ophthalmology, Hamilton Eye Institute, UTHSC, Memphis, Tennessee, United States
    Microbiology, Immunology and Biochemistry, UTHSC, Memphis, Tennessee, United States
  • Footnotes
    Commercial Relationships   Madison Ritter, None; William Coppess, None; Zachary Goldsmith, None; Rachel Brennan, None; Matthew Wilson, None; Vanessa Morales, None
  • Footnotes
    Support  Research to Prevent Blindness
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1779. doi:
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    • Get Citation

      Madison Ritter, William Coppess, Zachary K. Goldsmith, Rachel Brennan, Matthew W Wilson, Vanessa Marie Morales; Inhibition of PDGFR-β Decreases Pro-Survival Signaling of Retinoblastoma in vitro. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1779.

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

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Abstract

Purpose : Retinoblastoma (Rb) is the most common primary intraocular malignancy in children. Although highly treatable in the United States, there is a high mortality rate in developing countries due to metastatic disease. We have previously shown that signaling through platelet-derived growth factor receptor-beta (PDGFR-β) promotes invasiveness and survival of Rb and, when PDGFR-β is inhibited, there is a decrease in proliferation.

Methods : The well-characterized Y79 Rb cell line was used and represents the metastatic form of the disease. We investigated the role of the PDGFR-β in the control of cell survival by culturing cells in the presence of imatinib mesylate (IM), an inhibitor of kinases encoded by the BCR-ABL and PDGFR oncogenes. To address the effect of IM in cell death and survival, we measured the expression of both pro- and anti-apoptotic proteins, including AKT, BCL-2, and Caspase-3 by Western blot.

Results : We found a significant reduction in BCL-2 and AKT in Rb cells treated with IM. Moreover, we found an increase in Caspase-3 in IM-treated cells.

Conclusions : Our results are consistent with our hypothesis that inhibition of PDGFR-β impacts cell survival by reduction of the anti-apoptotic protein BCL-2 and the pro-survival molecule AKT while increasing Caspase-3.

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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