May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
IGFBP-3 Acts as a Hematopoietic Stem Cell Homing Factor in an Adult Mouse Ocular Neovascularization Model
Author Affiliations & Notes
  • J. L. Kielczewski
    University of Florida, Gainesville, Florida
    Pharmacology and Therapeutics,
  • A. Afzal
    University of Florida, Gainesville, Florida
    Pharmacology and Therapeutics,
  • K. Chang
    University of Florida, Gainesville, Florida
    Pharmacology and Therapeutics,
  • L. Shaw
    University of Florida, Gainesville, Florida
    Pharmacology and Therapeutics,
  • R. Mames
    Retina Center, Gainesville, Florida
  • E. McFarland
    Retinal Biology, University of Sydney, Sydney, Australia
  • T. Chan-Ling
    Retinal Biology, University of Sydney, Sydney, Australia
  • J. Hughes
    University of Florida, Gainesville, Florida
    Pharmaceutics,
  • M. Grant
    University of Florida, Gainesville, Florida
    Pharmacology and Therapeutics,
  • Footnotes
    Commercial Relationships  J.L. Kielczewski, None; A. Afzal, None; K. Chang, None; L. Shaw, None; R. Mames, None; E. McFarland, None; T. Chan-Ling, None; J. Hughes, None; M. Grant, None.
  • Footnotes
    Support  NIH1R01 EY07739, NIH R01EY12601, and the Juvenile Diabetes Research Foundation Grant 4-2000-847
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4389. doi:https://doi.org/
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      J. L. Kielczewski, A. Afzal, K. Chang, L. Shaw, R. Mames, E. McFarland, T. Chan-Ling, J. Hughes, M. Grant; IGFBP-3 Acts as a Hematopoietic Stem Cell Homing Factor in an Adult Mouse Ocular Neovascularization Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4389. doi: https://doi.org/.

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

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Abstract

Purpose: : IGFBP-3 has been shown to have direct pro-angiogenic effects on bone marrow derived hematopoietic stem cells and endothelial progenitor cells (EPC’s). IGFBP-3 stimulates HSC differentiation into endothelial cells and promotes their migration and tube formation in vitro. IGFBP-3 protects the retinal vasculature from oxygen induced damage by promoting vascular stability during hyperoxia exposure and vascular re-growth following return to room air in the oxygen induced retinopathy (OIR) model. In this study, we asked whether IGFBP-3 can also act as a homing factor for circulating HSC’s/EPC’s to establish residence in the retina. To test this we used an adult rodent ocular neovascularization model of laser induced retinal vessel occlusion.

Methods: : GFP+ chimeric mice were generated by isolating Sca-1+/c-Kit+ cells from GFP+ male mice via FACS sorting. Approximately 5,000 Sca-1+/c-Kit+ cells were injected into the retro-orbital sinus of 12 female mice. Stable engraftment was confirmed by flow cytometry 2 months following cell transplantation. The GFP+ stable chimeric mice were randomized into three treatment groups, laser only (n=4), IGFBP-3 injection only (n=4), and laser immediately followed by intravitreal injection of IGFBP-3 plasmid (n=4) (2ul of IGFBP-3 plasmid prepared in liposomes). The mice were sacrificed 3 weeks later. Flatmounts of the neural retina were prepared for retinal vessel visualization by immunohistochemisty and confocal microscopy.

Results: : Lasered mice treated with IGFBP-3 displayed large numbers of GFP+ cells incorporated into retinal vessels compared to fellow control eyes. Similarly mice treated with IGFBP-3 alone showed abundant numbers of GFP+ cells integrated into the retinal vessels even in the absence of laser induced retinal injury.

Conclusions: : IGFBP-3 can act as a HSC/EPC homing factor in an adult mouse neovascularization model. HSC’s can incorporate into retinal vessels and participate in repairing damaged vessels and contribute to the formation of new vessels.

Keywords: hypoxia • retinal neovascularization • growth factors/growth factor receptors 
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