Neurodegeneration and neuroprotection in glaucoma: development of a therapeutic neuroprotective vaccine: the Friedenwald lecture.

Glaucoma can be viewed as a neurodegenerative disease that is often associated with high intraocular pressure (IOP), and in which at any time there are fibers (optic nerve axons) and cell bodies (retinal ganglion cells) that are vulnerable to degeneration and amenable to protection. According to this view, patients receiving antihypertensive therapy to control an increase in intraocular pressure should also receive neuroprotective treatment that will circumvent, bypass, or reduce the threat to the neurons imposed by the degenerating neurons. Vaccination, proposed herein as a therapeutic measure, slows down disease propagation, in much the same way as it reduces secondary degeneration after acute insult to the rat optic nerve. The proposed vaccination is based on the unexpected discovery of “protective autoimmunity,” according to which a mechanical injury (optic nerve crush) or biochemical insult (glutamate toxicity in retinal ganglion cells) evokes a physiological autoimmune response which is specific to self-antigens residing in the site of damage and protects the nerve against the degenerative effects of glutamate and other destructive self-compounds. Protection was found to be boosted, without risk of autoimmune disease development, by vaccination with Cop-1, a synthetic antigenic copolymer which weakly cross-reacts with a broad spectrum of self-reactive (autoimmune) T cells, thus safely activating them for self repair. The proposed vaccination can therefore be viewed as a way of boosting the body’s physiological defense and repair mechanisms. Once its regimen and formulation are optimized for protection of retinal ganglion cells against death induced by an increase in IOP, Cop-1 can be immediately developed as a therapy for glaucoma.