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Hypoxia-regulated transgene expression in experimental retinal and choroidal neovascularization

Gene Therapy volume 10, pages 1049–1054 (2003)Cite this article

Abstract

Recombinant AAV vectors mediate efficient and sustained transgene expression in retinal tissues and offer a powerful approach to the local, sustained delivery of angiostatic proteins for the treatment of ocular neovascular disorders. The application of such strategies may also require regulated gene expression to minimize the potential for unwanted adverse effects. In this study, we have evaluated the effect of a hypoxia-responsive element (HRE) on the kinetics of recombinant adeno-associated (rAAV)-mediated reporter gene expression in murine models of retinal and choroidal neovascularization. In murine ischaemia-induced retinal neovascularization, intravitreal delivery of rAAV.HRE.GFP results in reporter gene expression specifically at sites of vascular closure during the period of active neovascularization and not after vector delivery in normal controls. In murine laser-induced choroidal neovascularization, subretinal delivery of rAAV.HRE.GFP results in reporter gene expression at sites of active neovascularization but not elsewhere or after vector delivery in normal controls. HRE-driven gene expression offers an attractive strategy for the targeted and regulated delivery of angiostatic proteins to the retina in the management of neovascular disorders.

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Acknowledgements

JWBB is a Wellcome Trust Research Training Fellow. AJT is a Wellcome Trust Senior Clinical Fellow. This work was also supported by Diabetes UK, Fight for Sight and the British Retinitis Pigmentosa Society.

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Authors and Affiliations

  1. Department of Molecular Genetics, Institute of Ophthalmology, University College London, London, UK

    J W B Bainbridge & R R Ali

  2. Molecular Immunology Unit, Institute of Child Health, University College London, London, UK

    A Mistry, M De Alwis, A J Thrasher & R R Ali

  3. Oxford Biomedica (UK) Ltd, Medawar Centre, Oxford Science Park, Oxford, UK

    K Binley & S Naylor

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  1. J W B Bainbridge
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  7. R R Ali
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Bainbridge, J., Mistry, A., Binley, K. et al. Hypoxia-regulated transgene expression in experimental retinal and choroidal neovascularization. Gene Ther 10, 1049–1054 (2003). https://doi.org/10.1038/sj.gt.3301945

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