April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Telomerase Inhibitor GRN163L as a Potential Antiangiogenic Agent for Neovascular Eye Diseases
Author Affiliations & Notes
  • R. Güngör
    Gata Goz Klinigi, Ankara, Turkey
  • Footnotes
    Commercial Relationships  R. Güngör, None.
  • Footnotes
    Support  GUNGOR SOBACI, MD
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 52. doi:
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      R. Güngör; Telomerase Inhibitor GRN163L as a Potential Antiangiogenic Agent for Neovascular Eye Diseases. Invest. Ophthalmol. Vis. Sci. 2009;50(13):52.

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

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Abstract

Purpose: : GRN163L (Geron Corporation, Menlo Park, CA, USA), is a lipid conjugated 13-mer N3’→P5’ thio-phosphoramidate oligonucleotide which is a potent telomerase RNA (hTR) template antagonist and thus inhibits the telomerase activity. It has been used in clinical trials for refractory, advanced solid tumors in the USA in recent years. It has been shown that telomerase activity is required for VEGF-dependent remodeling of ischemic tissue at the capillaries and arterioles level. This study aims to elucidate the antiangiogenic efficacy of GRN163L in vitro and in vivo angiogenesis models.

Methods: : In vitro experiments were performed at the research laboratory in the USA (Geron Co, Menlo Park, California), and in vivo experiments at the research laboratory in Turkey (GATA, Ankara). In in vitro experiments, TRAP (Telomeric repeat amplification protocol) assay was performed on HUVEC (Human Umbilical Vein Endothelial Cells) culture, and in vivo experiments on CAM (Chorio-Allontoic Membrane) model on day-12 to day-18.

Results: : GRN163L at 1µM or higher doses abrogated the telomerase activity of endothelial cells following 48 hours of incubation in vitro. Additionally, it inhibited the formation of new vessels completely on CAM assay when used at 5-10mg/kg (doses used in clinical trials).

Conclusions: : A telomerase template antagonist GRN163L has potential to become a novel antiangiogenic agent for neovascular eye diseases.

Keywords: neovascularization 
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