Purchase this article with an account.
S Bakalash, E Yoles, J Kipnis, T Mizrahi, M Schwartz; Designing Vaccination for Glaucoma: A new approach to neuroprotective therapy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1938.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Glaucoma is a chronic neurodegenerative disease of the optic nerve. It is reminiscent of other central nervous system (CNS) diseases in which neuroprotection can be conferred by the immune system. In this study we examined whether retinal ganglion cells (RGC's) death, induced by elevated intra ocular pressure (IOP), is immune dependent. We further assessed the efficacy of active immunization in protecting RGC's from IOP induced damage. Method: Two MHC-II matched rat strains were used, differing in their resistance to development of experimental autoimmune encephalomeyalitis (EAE). Elevated unilateral IOP was generated by argon laser photocoagulation of the episcleral veins and limbal plexus. Rats with elevated IOP were actively immunized with either synthetic copolymer Cop-1, peptides derived from CNS white matter, a uveitogenic peptide or PBS. To confirm immune involvement, EAE-susceptible rats were transferred with splenocytes from EAE-resistant rats. Control rats received either PBS or homologous splenocytes. The damage to RGC's was assessed 3 and 6 weeks after IOP induction, by retrograde labeling with Rodamine Dextran. Results: RGC count was significantly higher in EAE-resistant rats compared to EAE-susceptible rats both 3 weeks (1952±253.9 vs. 1419.7±272.3 RGC's/mm2 mean± stdev p=0.0006, respectively) and 6 weeks (1845.9±326.3 vs.1266.8±214.4 p=0.0002, respectively) after lasering. Splenocyte transfer from resistant to susceptible rats eliminated this difference (p=0.27). In both strains, damage induced by elevated IOP was reduced by vaccination with Cop-1 (2062.5±139 RGCs/mm2 compared to 1551±226 in control rats p=0.003 in the resistant strain, and 2301±139 vs. 1529±253 in susceptible rats, p=0.002). Similar results were obtained vaccinating with a uveitogenic peptide (2220.9±179.7 vs.1791.9±144.2 in control rats p=0.003), however, peptide antigens derived from white matter did not have any neuroprotective effect. Conclusion: In a rat model of chronically elevated IOP the ability to manifest a protective immune response is directly related to resistance to autoimmune disease development. Failure to promote neuroprotection with white matter antigens suggests that gray matter is primarily damaged and white matter is affected only in later stages of the disease. Neuroprotection achieved by vaccination with a uveitogenic peptide provides an insight as to the mechanism of retinal damage in anterior chamber disease, and may contribute to the design of future therapies for both glaucoma and uveitis.
This PDF is available to Subscribers Only