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T-cell-based vaccination for morphological and functional neuroprotection in a rat model of chronically elevated intraocular pressure

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An Erratum to this article was published on 11 August 2011

Abstract

Acute or chronic glaucoma is often associated with an increase in intraocular pressure (IOP). In many patients, however, therapeutic pressure reduction does not halt disease progression. Neuroprotection has been proposed as a complementary therapeutic approach. We previously demonstrated effective T-cell-based neuroprotection in experimental animals vaccinated with the synthetic copolymer glatiramer acetate (copolymer-1, Cop-1), a weak agonist of self-antigens. This study was undertaken to test different routes and modes of vaccination with Cop-1 as treatment modalities for protection against retinal ganglion cell (RGC) death caused by chronic elevation of IOP in rats, and to determine whether anatomical neuroprotection is accompanied by functional neuroprotection. In a chronic model of unilaterally high IOP, Cop-1 vaccination, with or without an adjuvant, protected rats against IOP-induced loss of RGCs by eliciting a systemic T-cell-mediated response capable of cross-reacting with self-antigens residing in the eye. In rats deprived of T cells, Cop-1 (unlike treatment with α2-adrenoreceptor agonists) was not protective of RGCs, substantiating the contention that its beneficial effect is not conferred directly but is T-cell-mediated. Pattern electroretinography provided evidence of functional protection. Thus, vaccination with adjuvant-free Cop-1 can protect RGCs from the consequences of elevated IOP in rats. This protection is manifested both morphologically and functionally. These findings can be readily implemented for the development of a therapeutic vaccination to arrest the progression of glaucoma.

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Acknowledgements

We thank S. Smith for editing the manuscript and A. Shapira for animal maintenance. M. Schwartz holds the Maurice and Ilse Katz Professorial Chair in Neuroimmunology. This work was supported in part by Teva Pharmaceutical Industries and in part by grants awarded to M. Schwartz by The Glaucoma Research Foundation and The Alan Brown Foundation for Spinal Cord Injury.

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Authors and Affiliations

  1. Department of Neurobiology, The Weizmann Institute of Science, 76100, Rehovot, Israel

    Sharon Bakalash, Iftach Shaked & Michal Schwartz

  2. Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot, Israel

    Gil Ben Shlomo & Ron Ofri

  3. Department of Ophthalmology, Kaplan Medical Center, Rehovot, Israel

    Eyal Aloni

  4. Department of Biological Sciences, Allergan Pharmaceuticals, Irvine, CA, USA

    Larry Wheeler

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  1. Sharon Bakalash
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  2. Gil Ben Shlomo
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  3. Eyal Aloni
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  4. Iftach Shaked
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  7. Michal Schwartz
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Correspondence to Michal Schwartz.

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An erratum to this article is available at http://dx.doi.org/10.1007/s00109-011-0789-4.

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Bakalash, S., Shlomo, G.B., Aloni, E. et al. T-cell-based vaccination for morphological and functional neuroprotection in a rat model of chronically elevated intraocular pressure. J Mol Med 83, 904–916 (2005). https://doi.org/10.1007/s00109-005-0689-6

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