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Redox proteins thioredoxin 1 and thioredoxin 2 support retinal ganglion cell survival in experimental glaucoma

Gene Therapy volume 16, pages 17–25 (2009)Cite this article

Abstract

We investigated the neuroprotective effect of thioredoxin 1 (Trx1) and thioredoxin 2 (Trx2) which play critical roles in the regulation of oxidative stress on retinal ganglion cells (RGCs) in a rat glaucoma model. Expression of Trx1 and Trx2 and Trx-interacting protein (Txnip) was observed in the RGC layer (GCL), nerve fiber layer and inner nuclear layer. Txnip-, Trx1- and Trx2-expressing cells in the GCL were primarily colocalized with RGCs. The increased Txnip protein level was observed 2 and 5 weeks after glaucoma induction. Trx1 level decreased 2 weeks after glaucoma induction and more prominently after 5 weeks. No change in Trx2 levels was detected. The effects of Trx1 and Trx2 overexpression on RGC survival were evaluated 5 weeks after glaucoma induction. In nontransfected and EGFP-transfected (used as a negative control) retinas, RGC loss was approximately 27% compared with control. The loss of RGCs in Trx1- and Trx2- transfected retinas was approximately 15 and 17%, respectively. Thus, Trx1 and Trx2 preserved 45 and 37% of cells, respectively that were destined to die in glaucomatous retinas. The results of this study provide evidence for the involvement of oxidative stress in RGC degeneration in experimental glaucoma and point to potential strategies to reduce its impact.

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Acknowledgements

We deeply thank Drs J Yodoi and H Masutani for providing Trx expression plasmids.

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Authors and Affiliations

  1. Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, USA

    Y Munemasa, J H Ahn, J M K Kwong, J Caprioli & N Piri

  2. Department of Ophthalmology, St Marianna University School of Medicine, Kawasaki, Japan

    Y Munemasa

  3. Brain Research Institute, University of California Los Angeles, Los Angeles, CA, USA

    J Caprioli & N Piri

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Correspondence to N Piri.

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Munemasa, Y., Ahn, J., Kwong, J. et al. Redox proteins thioredoxin 1 and thioredoxin 2 support retinal ganglion cell survival in experimental glaucoma. Gene Ther 16, 17–25 (2009). https://doi.org/10.1038/gt.2008.126

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