Regulation of Immune-Dependent Neuroprotection for Arresting Neuronal Degeneration in Optic Neuropathies

Abstract

Abstract: : Purpose: Neuroprotection (combined with pressure-reducing drugs) is now widely accepted as a promising potential therapy for glaucoma. Persuasive evidence indicates that immune activity, spontaneously evoked to help the optic nerve to cope with neurodegenerative conditions, is not sufficient on its own and can be therapeutically boosted by antigens residing in the site of the lesion. We examined the role of naturally occurring regulatory CD4+CD25+ T cells in the ability to manifest an anti-self protective response while avoiding autoimmune disease. Methods: Using models of optic nerve crush or intravitreal injection of toxic amounts of glutamate in two mouse strains differing in their ability to resist injurious conditions, as well as in nude mice (devoid of mature T cells), we assessed neuronal survival by counting the neurons that were retrogradely labeled with FluoroGold. Regulatory CD+CD25+ T cells were isolated from lymphoid organs of matched wild-type controls. Results: Mice deprived of regulatory T cells withstood the consequences of both insults significantly better than controls. The spontaneous response is evidently directed against abundant antigens residing in the site of damage. Neonatal immunization with myelin proteins or retinal proteins diminished the ability as adults to withstand insults directed to the optic nerve or to the retina, respectively. Conclusions: The ability to harness an immune response against self-antigens for the purpose of coping with mediators of optic neuropathies is apparently regulated by naturally occurring CD+CD25+ T cells, which allow expression of the protective activity of autoimmune T cells without inducing an autoimmune disease. These findings strongly encourage the development of a therapeutic vaccination against optic neuropathy as a way to boost a physiological remedy.

Keywords: neuroprotection • autoimmune disease • trauma