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

Sharon Bakalash, Gil Ben Shlomo, Eyal Aloni, Iftach Shaked, Larry Wheeler, Ron Ofri, Michal Schwartz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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 α 2-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.

Original languageAmerican English
Pages (from-to)904-916
Number of pages13
JournalJournal of Molecular Medicine
Volume83
Issue number11
DOIs
StatePublished - Nov 2005

Bibliographical note

Funding Information:
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.

Keywords

  • Glaucoma
  • Neurodegenerative diseases
  • Neuroprotection
  • Protective autoimmunity

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