title: Antigenic specificity of immunoprotective therapeutic vaccination for glaucoma.
abstract: OBJECTIVE
  To investigate the antigenic specificity of the immune neuroprotective mechanism that can protect retinal ganglion cells (RGCs) against death caused by high intraocular pressure (IOP).
  
  
  METHODS
  A unilateral increase in IOP was induced in rats by argon laser photocoagulation of the episcleral veins and limbal plexus. Rats with high IOP were immunized with glatiramer acetate (Cop-1, a synthetic copolymer) or with myelin-derived or uveitogenic peptides. When the steroid drug methylprednisolone was used, it was administered intraperitoneally every other day for 12 days.
  
  
  RESULTS
  Vaccination with myelin-derived peptides that reside in the axons failed to protect RGCs from death caused by high IOP. In contrast, IOP-induced RGC loss was reduced by vaccination with R16, a peptide derived from interphotoreceptor retinoid-binding protein, an immunodominant antigen residing in the eye. The benefit of protection against IOP-induced RGC loss outweighed the cost of the monophasic experimental autoimmune uveitis (EAU) that transiently developed in a susceptible rat strain. Treatment with methylprednisolone alleviated the disease symptoms, but caused further loss of RGCs. Cop-1 vaccination was effective in both EAU-resistant and EAU-susceptible strains.
  
  
  CONCLUSIONS
  To benefit damaged neurons, immune neuroprotection should be directed against immunodominant antigens that reside in the site of damage. In a rat model of high IOP, RGCs can benefit from vaccination with peptides derived from proteins that are immunodominant in the eye but not from myelin-associated proteins. This suggests that the site of primary degeneration in IOP-induced RGC loss is in the eye. Cop-1 vaccination apparently circumvents the site-specificity barrier and provides protection without risk of inducing autoimmune disease.
authors.affiliation: Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Bakalash
authors.forename: Anat
authors.initials: A
authors.lastname: Kessler
authors.forename: Tal
authors.initials: T
authors.lastname: Mizrahi
authors.forename: Robert
authors.initials: R
authors.lastname: Nussenblatt
authors.forename: Michal
authors.initials: M
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004195:Disease Models, Animal; D005136:Eye Proteins; D005901:Glaucoma / Q000473:pathology / Q000517:prevention & control*; D016056:Immunodominant Epitopes / Q000276:immunology*; D007429:Intraocular Pressure; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D004676:Myelin Basic Protein / Q000276:immunology; D009798:Ocular Hypertension / Q000517:prevention & control; D009842:Oligopeptides / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000276:immunology*; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000627:therapeutic use*; D000099214:Retinol-Binding Proteins, Interstitial
chemical_list: D005136:Eye Proteins; D016056:Immunodominant Epitopes; D008775:Methylprednisolone; D004676:Myelin Basic Protein; D009842:Oligopeptides; D012177:Retinol-Binding Proteins; D014614:Vaccines, Synthetic; D000099214:Retinol-Binding Proteins, Interstitial