Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 33, Pages 13444-13449Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0703707104
Keywords
combination therapy; neuroprotection; retinal ganglion cell apoptosis
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Funding
- Wellcome Trust [076947, GR076947, GR063658] Funding Source: Medline
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The development of the devastating neurodegenerative condition, Alzheimer's disease, is strongly associated with amyloid-beta (A beta) deposition, neuronal apoptosis, and cell loss. Here, we provide evidence that implicates these same mechanisms in the retinal disease glaucoma, a major cause of irreversible blindness worldwide, previously associated simply with the effects of intraocular pressure. We show that A beta colocalizes with apoptotic retinal ganglion cells (RGC) in experimental glaucoma and induces significant RGC apoptosis in vivo in a close- and time-dependent manner. We demonstrate that targeting different components of the A beta formation and aggregation pathway can effectively reduce glaucomatous RGC apoptosis in vivo, and finally, that combining treatments (triple therapy) is more effective than monotherapy. Our work suggests that targeting the A beta pathway provides a therapeutic avenue in glaucoma management. Furthermore, our work demonstrates that the combination of agents affecting multiple stages in the A beta pathway may be the most effective strategy in A beta-related diseases.
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