Antigenic specificity of immunoprotective therapeutic vaccination for glaucoma.
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.
Bakalash
Sharon
S
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
Kessler
Anat
A
Mizrahi
Tal
T
Nussenblatt
Robert
R
Schwartz
Michal
M
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
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