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In vivo use of oligonucleotides to inhibit choroidal neovascularisation in the eye

In vivo use of oligonucleotides to inhibit choroidal neovascularisation in the eye Background We have previously demonstrated the in vivo uptake of oligonucleotides in the rat eye and have continued with experiments to look at the effectiveness of targeted oligonucleotide sequences. Vascular endothelial growth factor (VEGF) is correlated with new blood vessel formation and has been implicated in numerous eye diseases characterised by abnormal blood vessel proliferation. An oligonucleotide targeted to the VEGF sequence was examined for its effect on VEGF production in vitro and the development of choroidal neovascularisation in vivo in the eye. Methods A series of sequences were assessed in an in vitro screening system using retinal pigment epithelial (RPE) cells to demonstrate a reduction in VEGF. A targeted sequence was further investigated using an animal model of choroidal neovascularisation where a krypton laser was used to produce a wound healing response in the choroid and retina. The oligonucleotide was injected into the vitreous and the development of choroidal neovascularisation assessed using fluorescein angiography. Results The targeted sequence was shown in vitro to downregulate the VEGF produced by RPE cells grown under hypoxic conditions and when injected into laser treated eyes was shown to be preferentially taken up in the laser lesion. Fluorescein angiography demonstrated that the test oligonucleotide was successful in reducing laser‐mediated choroidal neovascularisation. Conclusions A sequence corresponding to the 5′UTR of the VEGF gene has provided encouraging results for the treatment of neovascularisation. Copyright © 2001 John Wiley & Sons, Ltd. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Gene Medicine Wiley

In vivo use of oligonucleotides to inhibit choroidal neovascularisation in the eye

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References (28)

Publisher
Wiley
Copyright
Copyright © 2001 John Wiley & Sons, Ltd.
ISSN
1099-498X
eISSN
1521-2254
DOI
10.1002/jgm.197
pmid
11529667
Publisher site
See Article on Publisher Site

Abstract

Background We have previously demonstrated the in vivo uptake of oligonucleotides in the rat eye and have continued with experiments to look at the effectiveness of targeted oligonucleotide sequences. Vascular endothelial growth factor (VEGF) is correlated with new blood vessel formation and has been implicated in numerous eye diseases characterised by abnormal blood vessel proliferation. An oligonucleotide targeted to the VEGF sequence was examined for its effect on VEGF production in vitro and the development of choroidal neovascularisation in vivo in the eye. Methods A series of sequences were assessed in an in vitro screening system using retinal pigment epithelial (RPE) cells to demonstrate a reduction in VEGF. A targeted sequence was further investigated using an animal model of choroidal neovascularisation where a krypton laser was used to produce a wound healing response in the choroid and retina. The oligonucleotide was injected into the vitreous and the development of choroidal neovascularisation assessed using fluorescein angiography. Results The targeted sequence was shown in vitro to downregulate the VEGF produced by RPE cells grown under hypoxic conditions and when injected into laser treated eyes was shown to be preferentially taken up in the laser lesion. Fluorescein angiography demonstrated that the test oligonucleotide was successful in reducing laser‐mediated choroidal neovascularisation. Conclusions A sequence corresponding to the 5′UTR of the VEGF gene has provided encouraging results for the treatment of neovascularisation. Copyright © 2001 John Wiley & Sons, Ltd.

Journal

Journal of Gene Medicine – Wiley

Published: Jul 1, 2001

Keywords: VEGF; choroidal neovascularisation; oligonucleotides; eye

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