Synucleins are small proteins associated with neurodegenerative diseases and some forms of cancer. They are studied predominantly in the brain; information about their presence and functions in ocular tissues is scarce. Here we describe the localization of three members of the synuclein family in the optic nerve of donors with different types of glaucoma compared with control samples from donors without ocular diseases. We did not find significant differences in the localization of α- and β-synucleins in the optic nerve or retina of glaucoma patients compared with controls, whereas considerable redistribution of γ-synuclein occurred in the glaucomatous optic nerve compared with control eye without glaucoma. In the optic nerve from control and glaucomatous individuals, nerve bundles are immunopositive for γ-synuclein; however, a strong γ-synuclein-immunopositive staining in a subset of glial cells was observed in the lamina and postlamina cribrosa regions of the optic nerve only in glaucoma patients. In the optic nerve of rats with episcleral vein cauterization used as an animal model of glaucoma, the quantity of both γ-synuclein mRNA and protein was decreased compared with the optic nerves of control animals. Incubation of rat astrocyte culture at elevated hydrostatic pressure reduced the amount of γ-synuclein but did not affect the quantities of actin and glial fibrillary acidic protein. These data suggest that significant changes in the pattern of expression and/or localization occur in the glaucomatous optic nerve for γ-synuclein but not for α- and β-members of the synuclein family. © 2002 Wiley-Liss, Inc.