Dysregulation of intraocular pressure (IOP) is one of the main risk factors for
glaucoma. γ-
synuclein is a member of the
synuclein family of widely expressed synaptic
proteins within the central nervous system that are implicated in certain types of neurodegeneration. γ-
synuclein expression and localization changes in the retina and optic nerve of patients with
glaucoma. However, the mechanisms by which γ-
synuclein could contribute to
glaucoma are poorly understood. We assessed the presence of
autoantibodies to γ-
synuclein in the blood serum of patients with
primary open-angle glaucoma (POAG) by immunoblotting. A positive reaction was detected for five out of 25 patients (20%) with POAG.
Autoantibodies to γ-
synuclein were not detected in a group of patients without
glaucoma. We studied the dynamics of IOP in response to IOP regulators in knockout mice (γ-KO) to understand a possible link between γ-
synuclein dysfunction and
glaucoma-related pathophysiological changes. The most prominent decrease of IOP in γ-KO mice was observed after the instillation of 1%
phenylephrine and 10%
dopamine. The total
protein concentration in tear fluid of γ-KO mice was approximately two times higher than that of wild-type mice, and the activity of neurodegeneration-linked
protein α2-macroglobulin was reduced. Therefore, γ-
synuclein dysfunction contributes to
pathological processes in
glaucoma, including dysregulation of IOP.