Glaucoma: ocular Alzheimer's disease?

Published online

Journal Article (Review)

Glaucoma is a chronic neurodegeneration of the optic nerve and one of the leading causes of vision loss in the world among the aging. Retinal ganglion cells (RGCs) have been shown to die by apoptosis, or programmed cell death. Central to apoptosis is the activation of specific proteases, termed caspases. Caspases are activated in chronic neurodegenerations such as Alzheimer's disease (AD) as well as in RGCs after optic nerve transection. In rat glaucoma models we have shown that caspase-3, a major effector of the apoptotic cascade, is activated in RGCs and cleaves amyloid precursor protein (APP) to produce neurotoxic fragments that include amyloid-beta. Caspase-8, which initiates apoptosis after activation of receptors of the tumor necrosis factor (TNF) superfamily, is also activated in RGCs. This suggests a new hypothesis for RGC death in glaucoma involving chronic amyloid-beta neurotoxicity, mimicking AD at the molecular level. With loss of the protective effect of APP and upregulation of toxic APP fragments, RGCs die from chronic caspase activation, loss of synaptic homeostasis, amyloid-beta cytotoxicity and excitotoxicity. The benefits are that treatments for AD could be used to treat glaucoma, and strategies developed to treat glaucoma could treat other neurodegenerations.

Full Text

Duke Authors

Cited Authors

  • McKinnon, SJ

Published Date

  • September 1, 2003

Published In

Volume / Issue

  • 8 /

Start / End Page

  • s1140 - s1156

PubMed ID

  • 12957857

Pubmed Central ID

  • 12957857

International Standard Serial Number (ISSN)

  • 1093-9946

Digital Object Identifier (DOI)

  • 10.2741/1172

Language

  • eng

Conference Location

  • United States