April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Treatment of Choroidal Neovascularization Using Nanoparticle Coupled to Integrin vβ3-Targeted Gene Delivery System
Author Affiliations & Notes
  • M. Roh
    Ophthalmology, Angiogenesis Laboratory,Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • A. Giani
    Ophthalmology, Angiogenesis Laboratory,Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • D. Vavvas
    Ophthalmology, Angiogenesis Laboratory,Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • J. W. Miller
    Ophthalmology, Angiogenesis Laboratory,Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • S. Guccione
    Radiology, RSL Lucas Center, Standford University, Palo Alto, California
  • H. Salehi-Had
    Ophthalmology, Angiogenesis Laboratory,Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  M. Roh, None; A. Giani, None; D. Vavvas, None; J.W. Miller, None; S. Guccione, None; H. Salehi-Had, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4948. doi:
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      M. Roh, A. Giani, D. Vavvas, J. W. Miller, S. Guccione, H. Salehi-Had; Treatment of Choroidal Neovascularization Using Nanoparticle Coupled to Integrin vβ3-Targeted Gene Delivery System. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4948.

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

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Abstract

Purpose: : We previously showed that αvβ3 integrin-ligand coupled cationic nanoparticle (NP) is able to bind to and deliver a green fluorescing protein plasmid to the abnormal endothelial cells of the laser induced choroidal neovascularization(CNV) in rats. Therefore, we would like to investigate the therapeutic efficacy of αvβ3 integrin-ligand coupled cationic NP containing a dominant negative Raf mutant gene (ATPµ-Raf) in laser-induced CNV.

Methods: : CNV lesions were induced in Brown Norway rats using laser photocoagulation. In the treatment group, rats received intravenous NP(1mg/kg) containing ATPµ-Raf(1µg/kg, total volume 350 µl)on days 1, 3, and 5 after laser photocoagulation. In the control group, rats received no treatment, injection with nontargeted NP containing ATPµ-Raf, injection with ATPµ-Raf only, and injection with αvβ3 integrin-ligand coupled cationic NP only. CNV were examined by fundus fluorescein angiography on days 7 and 14 and by FITC-dextran flat mounts on day 14. TUNEL positive cells were quantified in the outer nuclear layer and CNV in cyrosections on day 7 and 14.

Results: : Flatmount analysis showed that NP with ATPµ-Raf significantly decreased the surface area of laser-induced CNV by 27.3 % compared with vehicle treated control animals (P<0.001). Moreover, NP with ATPµ-Raf treated animals had significantly fewer TUNEL-positive cells in the photoreceptor layer than did the control animals (P < 0.05).

Conclusions: : Systemic administration of αvβ3-targeted delivery of ATPµ-Raf via nanoparticles leads to reduced size and leakage of laser induced CNV.

Keywords: choroid: neovascularization • laser • apoptosis/cell death 
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