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XIAP-mediated neuroprotection in retinal ischemia

Gene Therapy volume 13, pages 339–347 (2006)Cite this article

Abstract

Retinal ischemia results in the loss of vision in a number of ocular diseases including acute glaucoma, diabetic retinopathy, hypertensive retinopathy and retinal vascular occlusion. Recent studies have shown that most of the neuronal death that leads to loss of vision results from apoptosis. XIAP-mediated gene therapy has been shown to protect a number of neuronal types from apoptosis but has never been assessed in retinal neurons following ischemic-induced cell death. We injected an adeno-associated viral vector expressing XIAP or GFP into rat eyes and 6 weeks later, rendered them ischemic by raising intraocular pressure. Functional analysis revealed that XIAP-treated eyes retained larger b-wave amplitudes than GFP-treated eyes up to 4 weeks post-ischemia. The number of cells in the inner nuclear layer (INL) and the thickness of the inner retina were significantly preserved in XIAP-treated eyes compared to GFP-treated eyes. Similarly, there was no significant reduction in optic nerve axon numbers in XIAP-treated eyes. There were also significantly fewer TUNEL (TdT-dUTP terminal nick end labeling) positive cells in the INL of XIAP-treated retinas at 24 h post-ischemia. Thus, XIAP-mediated gene therapy imparts both functional and structural protection to the retina after a transient ischemic episode.

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Acknowledgements

We are grateful to Dr Peter Liston for reagents and Sandra L Hurley, Sarah Ikeda, Brendan Joyce and Vince Chiodo for technical assistance. We also thank Louise Pelletier for processing optic nerve cross-sections for our studies, Isabelle Gaboury for assistance with statistical analysis and Drs Rashmi Kothari and Valerie Wallace for analysis of glial tissue infiltration of optic nerve cross-sections. These studies were supported by a Grant from the Canadian Institute for Health Research (CIHR). WWH and the University of Florida could be entitled to patent royalties for inventions related to this work and both own equity in a company that may commercialize some of the technology described herein.

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Author notes

  1. J Renwick and M A Narang: These two authors made equally significant contributions to this work.

Authors and Affiliations

  1. University of Ottawa Eye Institute, Ottawa, Ontario, Canada

    J Renwick, M A Narang, S G Coupland, J Y Xuan, A N Baker, J Brousseau, D Petrin, R Munger, B C Leonard & C Tsilfidis

  2. University of Florida College of Medicine, Gainesville, FL, USA

    W W Hauswirth

  3. Solange-Gauthier-Karsh Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada

    R G Korneluk

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  1. J Renwick
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  2. M A Narang
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  3. S G Coupland
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Correspondence to C Tsilfidis.

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Renwick, J., Narang, M., Coupland, S. et al. XIAP-mediated neuroprotection in retinal ischemia. Gene Ther 13, 339–347 (2006). https://doi.org/10.1038/sj.gt.3302683

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