T-cell-based vaccination for morphological and functional neuroprotection in a rat model of chronically elevated intraocular pressure.
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 alpha2-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.
Bakalash
Sharon
S
Department of Neurobiology, The Weizmann Institute of Science, 76100, Rehovot, Israel, michal.schwartz@weizmann.ac.il.
Ben-Shlomo
Gil
G
Shlomo
Gil Ben
GB
Aloni
Eyal
E
Shaked
Iftach
I
Wheeler
Larry
L
Ofri
Ron
R
Schwartz
Michal
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D055511:CCN Intercellular Signaling Proteins; D019610:Cytoprotection / Q000276:immunology; D004195:Disease Models, Animal; D004596:Electroretinography; D007429:Intraocular Pressure / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination
D000276:Adjuvants, Immunologic; D055511:CCN Intercellular Signaling Proteins; C115044:CCN5 protein, rat; D009883:Ophthalmic Solutions; D012097:Repressor Proteins