Impaired regulatory T cell mediated immune tolerance promotes neurodegeneration in glaucoma

The study addresses whether failure of peripheral immune tolerance actively contributes to neuronal loss in chronic neurodegeneration, a link that has remained unclear. Using primary open-angle glaucoma as a model, the authors tested whether dysregulated adaptive immunity is sufficient to promote retinal ganglion cell degeneration.

Peripheral blood mononuclear cells from glaucoma patients, but not from healthy donors, induced retinal ganglion cell loss after transfer into humanized immunodeficient mice. This occurred without changes in intraocular pressure, supporting a causal role for immune responses in the patient-derived material rather than pressure-mediated injury.

Comprehensive immune profiling showed selective changes in the regulatory T-cell compartment: reduced activation, an impaired suppressive phenotype, and altered differentiation and trafficking states, even though overall regulatory T-cell abundance was preserved. In an experimental glaucoma model, transient expansion of regulatory T cells preserved visual function, reduced optic nerve axonal degeneration, and limited retinal ganglion cell loss.

Together, the findings identify failure of regulatory T-cell-mediated immune tolerance as a mechanism that permits neurodegeneration in glaucoma and show that restoring immune regulation can ameliorate neuronal injury. The authors conclude that immune tolerance is a modifiable determinant of chronic neurodegeneration and suggest immunoregulatory therapies may complement conventional pressure-lowering treatments to preserve vision in glaucoma.