September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Evaluation of cytotoxicity of Pazopanib on proliferation of vascular endothelial growth factor enriched choroidal vascular endothelial cells
Author Affiliations & Notes
  • K .V. Chalam
    Ophthalmology , University of Florida, Jacksonville , Florida, United States
  • Bharani Krishna Mynampati Arunadithya
    Ophthalmology , University of Florida, Jacksonville , Florida, United States
  • Kumar Sambhav
    Ophthalmology , University of Florida, Jacksonville , Florida, United States
  • Footnotes
    Commercial Relationships   K .V. Chalam, None; Bharani Krishna Mynampati Arunadithya, None; Kumar Sambhav, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3339. doi:
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      K .V. Chalam, Bharani Krishna Mynampati Arunadithya, Kumar Sambhav; Evaluation of cytotoxicity of Pazopanib on proliferation of vascular endothelial growth factor enriched choroidal vascular endothelial cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3339.

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

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Abstract

Purpose : Ranibizumab, Bevacizumab and Aflibercept are currently approved anti vascular endothelial growth factor (VEGF) agents for the managment of exudative age related macular degeneration (AMD). However they are expensive and need repeated intravitreal injections due to limited duration of action. Pazopanib (FDA approved), a tyrosine kinase inhibitor that blocks the receptors of VEGF is effective in management of renal cell carcinoma. through inhibition of VEGF. In this study we evaluated the cytotoxicity of varying doses of Pazopanib on VEGF enriched choroidal vascular endothelial cells (CVECs)

Methods : Proliferating CVECs (enriched with VEGF 50 ng/ml)were treated with escalating doses of pazopanib (10,50,100,250 µM). Cell proliferation changes were analyzed with water soluble tetrazolium salts (WST-1) assay. Cytotoxicity in response to pazopanib was evaluated with trypan blue exclusion assay at 48h, 72h, 1week. Simultaneously reactive oxygen species levels were measured using dihydrorhodamine 123 at similar intervals. Human retinal pigment epithelial cells (HRPEs) served as controls.

Results : Pazopanib inhibited the proliferation of VEGF enriched CVECs treated with varying doses of pazopanib (10, 50, 100, 250 µM) in a dose and time dependent manner. CVECs showed a significant decrease in the cell proliferation after one week treatment with pazopanib compared to controls. The CVECs showed a decrease in cell proliferation by 12.2 %( p<0.0001), 57% (p<0.0001), 61.9% (p<0.0001), 90.7% (p<0.0001) in comparison to control cells respectively with WST-1 assay. Trypan blue exclusion assay also revealed similar decrease in CVECs proliferation 18.2% (p=0.24), 19% (p=0.21), 46.6% (p=0.0014), 91.3% (p<0.0001) compared to control cells. Reactive oxygen species levels increased significantly in CVECs in a dose dependent manner i.e 138.6% (p=0.02), 148.9% (p=0.003), 153.9% (p=0.001), and 169.9% (p<0.0001) respectively compared to control cells.

Conclusions : Pazopanib inhibited cell proliferation of VEGF enriched CVECs significantly compared to controls in a dose and time dependent fashion and can be potentially effective in controlling subretinal choroidal neovascular membrane associated with AMD.

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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