Purchase this article with an account.
S. Bakalash, G. Ben Simon, M. Schwartz; A New Route for Therapeutic Intervention: Topical Vaccination for Acute and Chronic Glaucoma . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2151.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the optimal route and dosage of Cop-1 vaccination for protection of retinal ganglion cells (RGCs) from death caused by high intraocular pressure (IOP) in acute and chronic rat models of glaucoma, a chronic neurodegenerative disease of the optic nerve. Poly-EY, a copolymer of glutamate and tyrosine, was also tested. Methods: IOP in rats was elevated by argon laser photocoagulation of the episcleral and limbal veins (chronic model) or by infusion (1 hour) of normal saline (0.9%) into the anterior chamber via a 30-gauge needle (acute model). IOP was measured using a Tono-Pen tonometer (XL, Mentor). Cop-1, poly-EY, or PBS (control) was administered at different time intervals, dosages, and routes. IOP-generated damage was assessed after 1 or 2 weeks (acute model) and after 3 weeks (chronic model) by retrograde labeling of viable RGCs with rhodamine dextran. Results: Nerve damage in both models was reduced by Cop-1 or poly-YE vaccination. In the acute model, Cop-1 in complete Freund's adjuvant (CFA) reduced RGC death from 45.7%±8.2% (control) to 12.6%±4. 9% (P<0.0001). This effect persisted even when high IOP lasted for 12 weeks (57.2%±6.3% versus 33.7%±2.4, respectively, P<0.001). Subcutaneous immunization of each polymer without adjuvant also reduced RGC death. In the acute model, a single topical vaccination (corrected for dosage) induced neuroprotection as effectively as other administration routes (RGC death was 31.5%±4.7% with poly EY, 31.0%±3.2% with Cop-1, and 58.6%±7.5% in control; P<0.001). Vaccination of T cell-deprived rats was ineffective, supporting the notion that the protection is immune mediated. Conclusions: In rat models of acute and chronic glaucoma, RGC protection is immune mediated and can be obtained by vaccination with or without adjuvant. Vaccination is effective even if delayed, and has a long-lived effect despite persistence of pressure-induced degeneration. Vaccinating with compounds such as Cop-1 and YE without adjuvant obviates the risk of autoimmune disease induction. Topical immunization represents a unique mode of therapy for eye-related and possibly also other neurodegenerative diseases.
This PDF is available to Subscribers Only