A role of pigment epithelium-derived factor in zinc-mediated mechanism of neurodegeneration in glaucoma.

ABSTRACT: Glaucoma is a neurodegenerative condition involving optic nerve damage and retinal ganglion cells death. Animal studies suggested that the pathway linking these events can be mediated by mobile zinc secreted into the intraretinal space and exerting cytotoxic effects. Whether this mechanism is relevant for human glaucoma and what are the targets of extracellular zinc is unknown. We report that increased zinc content in the aqueous humor and retina is indeed a characteristic of glaucomatous neuropathy, and excess extracellular zinc may be recognized by the key retinal neurotrophic factor PEDF. Biophysical and X-ray crystallographic studies show that PEDF coordinates zinc ions in five types of intermolecular high-affinity sites, leading to a decrease in negative surface charge and reversible

SUBMITTER: Chistyakov DV 

PROVIDER: S-EPMC12215840 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature