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Anti-apoptotic gene therapy prolongs survival of corneal endothelial cells during storage

Gene Therapy volume 18, pages 778–787 (2011)Cite this article

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Abstract

Corneal transplantation is the most common form of grafting performed worldwide. Corneal endothelial cells (EC) form a monolayer in the posterior portion of the cornea and are essential for corneal transparency. EC loss during storage before transplantation is a principal reason for rendering donor tissue unsuitable for transplantation, and apoptosis has been shown to be the major contributor to EC loss during storage and after transplantation. Therefore, the potential use of anti-apoptotic gene therapy to promote both graft storage and graft survival is of major interest. The goal of this study was to transduce human donor corneas in vitro to enhance EC survival during storage conditions used in eye banking. We utilized a lentiviral vector to perform gene transfer of baculoviral p35 or mammalian Bcl-xL to corneal endothelium in different storage conditions utilizing a lentiviral vector. Our results show significantly enhanced survival and prolonged retention of physiological EC morphology in cells expressing either p35 or Bcl-xL. The clinical application of this technology could lead to a higher availability of donor tissue for transplantation, extend storage periods and reduce graft failure after transplantation.

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Acknowledgements

This work was supported by NIH R01EY012963 (RD), K24EY019098 (RD), Research to Prevent Blindness Lew R. Wasserman Merit Award (RD), the German Research Foundation (DFG/FU 726/1-1, TF) and the Eye Bank Association of America (TF). We thank Tissue Banks International and the Lions Eye Institute for Transplant and Research (Tampa, Florida) for providing corneas for research purposes. We thank Kim Fechtel, PhD, for the critical review of the manuscript.

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Authors and Affiliations

  1. Department of Ophthalmology, The Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA

    T A Fuchsluger, U Jurkunas, A Kazlauskas & R Dana

  2. Center of Ophthalmology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany

    T A Fuchsluger

  3. Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA

    U Jurkunas & R Dana

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  1. T A Fuchsluger
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Correspondence to R Dana.

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Competing interests

The Schepens Eye Research Institute and the University of Duisburg-Essen filed a patent cooperative treaty to protect rights emanating from this work. Dr Kazlauskas received compensation in 2009 from Celegene. Dr Fuchsluger, Dr Jurkunas and Dr Dana have nothing to disclose.

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Fuchsluger, T., Jurkunas, U., Kazlauskas, A. et al. Anti-apoptotic gene therapy prolongs survival of corneal endothelial cells during storage. Gene Ther 18, 778–787 (2011). https://doi.org/10.1038/gt.2011.20

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